Dépendance – Wikipédia

Dependance Wikipedia - Dépendance - Wikipédia

Maladie entraînant un engagement compulsif dans des stimuli gratifiants malgré des conséquences néfastes

État de santé

Lexique des addictions et dépendances(3)(4)(5)(2)
  • dépendance – un trouble biopsychosocial caractérisé par une consommation persistante de drogues (dont l'alcool) malgré des dommages importants et des conséquences néfastes
  • drogue addictive – les substances psychoactives qui, avec une utilisation répétée, sont associées à des taux significativement plus élevés de troubles liés à l'utilisation de substances, en grande partie en raison de l'effet de la drogue sur les systèmes de récompense du cerveau
  • dépendance – un état adaptatif associé à un syndrome de sevrage lors de l'arrêt de l'exposition répétée à un stimulus (par exemple, prise de médicament)
  • sensibilisation aux médicaments ou alors tolérance inverse – l’escalade de l’effet d’un médicament résultant de l’administration répétée à une dose donnée
  • sevrage médicamenteux – symptômes qui surviennent lors de l’arrêt de l’usage répété de drogues
  • dépendance physique – dépendance qui implique des symptômes de sevrage physiques et somatiques persistants (par exemple, fatigue et delirium tremens)
  • dépendance psychologique – dépendance qui implique des symptômes de sevrage émotionnel-motivation (par exemple, dysphorie et anhédonie)
  • stimuli de renforcement – des stimuli qui augmentent la probabilité de répéter les comportements qui leur sont associés
  • stimuli enrichissants – des stimuli que le cerveau interprète comme intrinsèquement positifs et désirables ou comme quelque chose à approcher
  • sensibilisation – une réponse amplifiée à un stimulus résultant d'une exposition répétée à celui-ci
  • trouble de consommation de substances – une condition dans laquelle la consommation de substances entraîne une altération ou une détresse cliniquement et fonctionnellement significative
  • tolérance – l’effet diminuant d’un médicament résultant de l’administration répétée à une dose donnée

Dépendance est un trouble cérébral caractérisé par un engagement compulsif dans des stimuli gratifiants malgré des conséquences néfastes.(3)(5)(2)(6)(7)(8) Malgré l'implication d'un certain nombre de facteurs psychosociaux, un processus biologique – qui est induit par une exposition répétée à un stimulus addictif – est la pathologie centrale qui entraîne le développement et le maintien d'une dépendance, selon le « modèle de maladie du cerveau » de la dépendance. .(3) Cependant, certains chercheurs qui étudient la toxicomanie soutiennent que le modèle de la maladie cérébrale est incomplet et trompeur.(9)(dix)(11)(12)(13)(14)

Le modèle des maladies cérébrales postule que la dépendance est un trouble du système de récompense du cerveau qui survient par le biais de mécanismes transcriptionnels et épigénétiques et se développe au fil du temps à partir de niveaux chroniquement élevés d'exposition à un stimulus addictif (p. activité, participation à des activités culturelles à sensations fortes comme le jeu, etc.).(3)(15)(16) DeltaFosB (ΔFosB), un facteur de transcription génique, est un élément essentiel et un facteur commun dans le développement de pratiquement toutes les formes de toxicomanie comportementale et de toxicomanie.(15)(16)(17)(18) Deux décennies de recherche sur le rôle de FosB dans la toxicomanie ont démontré que la dépendance survient et que le comportement compulsif associé s'intensifie ou s'atténue, ainsi que la surexpression de osFosB dans les neurones épineux moyens de type D1 du noyau accumbens.(3)(15)(16)(17) En raison de la relation causale entre l'expression de ΔFosB et les dépendances, il est utilisé en préclinique comme biomarqueur de dépendance.(3)(15)(17) L'expression de ΔFosB dans ces neurones régule directement et positivement l'auto-administration du médicament et la sensibilisation à la récompense par le renforcement positif, tout en diminuant la sensibilité à l'aversion.(note 1)(3)(15)

La toxicomanie impose un "péage financier et humain incroyablement élevé" sur les individus et la société dans son ensemble.(19)(20)(21) Aux États-Unis, le coût économique total pour la société est supérieur à celui de tous les types de diabète et de tous les cancers réunis.(21) Ces coûts découlent des effets indésirables directs des médicaments et des coûts de santé associés (par exemple, les services médicaux d'urgence et les soins ambulatoires et hospitaliers), les complications à long terme (par exemple, le cancer du poumon dû à la consommation de produits du tabac, la cirrhose du foie et la démence due à la consommation chronique d'alcool, et méthamphétamine buccale due à la consommation de méthamphétamine), la perte de productivité et les coûts de bien-être associés, les accidents mortels et non mortels (par exemple, les collisions routières), les suicides, les homicides et l'incarcération, entre autres.(19)(20)(21)(22) Les caractéristiques classiques de la toxicomanie comprennent une altération du contrôle des substances ou du comportement, une préoccupation pour une substance ou un comportement et une utilisation continue malgré les conséquences.(23) Les habitudes et les schémas associés à la dépendance sont généralement caractérisés par une gratification immédiate (récompense à court terme), associée à des effets délétères retardés (coûts à long terme).(24)

Des exemples de toxicomanie et de dépendance comportementale comprennent l'alcoolisme, la dépendance à la marijuana, la dépendance aux amphétamines, la dépendance à la cocaïne, la dépendance à la nicotine, la dépendance aux opioïdes, la dépendance alimentaire, la dépendance au chocolat, la dépendance aux jeux vidéo, la dépendance au jeu et la dépendance sexuelle. La seule dépendance comportementale reconnue par le DSM-5 et l'ICD-10 est la dépendance au jeu. Avec l'introduction de la CIM-11, la dépendance au jeu a été ajoutée.(25) Le terme dépendance est fréquemment utilisé à mauvais escient pour désigner d'autres comportements ou troubles compulsifs, en particulier dépendance, dans les médias d'information.(26) Une distinction importante entre la toxicomanie et la dépendance est que la toxicomanie est un trouble dans lequel l'arrêt de la consommation de drogue entraîne un état de sevrage désagréable, qui peut conduire à une consommation de drogue supplémentaire.(27) La toxicomanie est l'utilisation compulsive d'une substance ou l'accomplissement d'un comportement indépendant du sevrage. La toxicomanie peut survenir en l'absence de dépendance, et la dépendance peut survenir en l'absence de toxicomanie, bien que les deux se produisent souvent ensemble.

Neuropsychologie(Éditer)

Le contrôle cognitif et le contrôle du stimulus, qui sont associés au conditionnement opérant et classique, représentent des processus opposés (c'est-à-dire internes vs externes ou environnementaux, respectivement) qui rivalisent pour le contrôle des comportements suscités par un individu.(28) Le contrôle cognitif, et en particulier le contrôle inhibiteur du comportement, est altéré à la fois dans la dépendance et le trouble d'hyperactivité avec déficit de l'attention.(29)(30) Les réponses comportementales induites par le stimulus (c'est-à-dire le contrôle du stimulus) qui sont associées à un stimulus gratifiant particulier ont tendance à dominer le comportement d'une personne dans une dépendance.(30)

Contrôle du stimulus par le comportement(Éditer)

Contrôle cognitif du comportement(Éditer)

Dépendance comportementale(Éditer)

Le terme dépendance comportementale fait référence à une compulsion à s'engager dans une récompense naturelle – qui est un comportement qui est intrinsèquement gratifiant (c'est-à-dire souhaitable ou attrayant) – malgré les conséquences négatives.(7)(16)(18) Des preuves précliniques ont démontré qu'une augmentation marquée de l'expression de ΔFosB par une exposition répétitive et excessive à une récompense naturelle induit les mêmes effets comportementaux et neuroplasticité que ceux observés dans une toxicomanie.(16)(31)(32)(33)

Les examens de la recherche clinique chez l'homme et des études précliniques impliquant ΔFosB ont identifié l'activité sexuelle compulsive – en particulier, toute forme de rapport sexuel – comme une dépendance (c'est-à-dire une dépendance sexuelle).(16)(31) De plus, la sensibilisation croisée de récompense entre l'amphétamine et l'activité sexuelle, ce qui signifie que l'exposition à l'une augmente le désir des deux, s'est avérée se produire de manière préclinique et clinique en tant que syndrome de dérégulation de la dopamine ;(16)(31)(32)(33) L'expression de FosB est requise pour cet effet de sensibilisation croisée, qui s'intensifie avec le niveau d'expression de ΔFosB.(16)(32)(33)

Des revues d'études précliniques indiquent qu'une consommation fréquente et excessive à long terme d'aliments riches en graisses ou en sucre peut produire une dépendance (dépendance alimentaire).(16)(18) Cela peut inclure du chocolat. La saveur sucrée et les ingrédients pharmacologiques des chocolats sont connus pour créer une forte envie ou une sensation de « dépendance » chez le consommateur.(34) Une personne qui aime beaucoup le chocolat peut se considérer comme un accro au chocolat. Le chocolat n'est pas encore formellement reconnu par le DSM-5 comme une dépendance pouvant être diagnostiquée.(35)

Le jeu offre une récompense naturelle qui est associée à un comportement compulsif et pour laquelle les manuels de diagnostic clinique, à savoir le DSM-5, ont identifié des critères de diagnostic pour une "addiction".(16) Pour que le comportement de jeu d'une personne réponde aux critères d'une dépendance, il présente certaines caractéristiques, telles que la modification de l'humeur, la compulsivité et le retrait. Il existe des preuves issues de la neuroimagerie fonctionnelle que le jeu active le système de récompense et la voie mésolimbique en particulier.(16)(36) De même, faire du shopping et jouer à des jeux vidéo sont associés à des comportements compulsifs chez les humains et il a également été démontré qu'ils activent la voie mésolimbique et d'autres parties du système de récompense.(16) Sur la base de ces preuves, la dépendance au jeu, la dépendance aux jeux vidéo et la dépendance au shopping sont classées en conséquence.(16)(36)

Facteurs de risque(Éditer)

Il existe un certain nombre de facteurs de risque génétiques et environnementaux pour développer une dépendance, qui varient selon la population.(3)(37) Les facteurs de risque génétiques et environnementaux représentent chacun environ la moitié du risque d'un individu de développer une dépendance;(3) la contribution des facteurs de risque épigénétiques au risque total est inconnue.(37) Même chez les personnes présentant un risque génétique relativement faible, l'exposition à des doses suffisamment élevées d'une drogue addictive pendant une longue période (par exemple, des semaines à des mois) peut entraîner une dépendance.(3)

Facteurs génétiques(Éditer)

Il est établi depuis longtemps que les facteurs génétiques ainsi que les facteurs environnementaux (par exemple, psychosociaux) contribuent de manière significative à la vulnérabilité à la toxicomanie.(3)(37) Des études épidémiologiques estiment que les facteurs génétiques représentent 40 à 60 % des facteurs de risque d'alcoolisme.(38) Des taux similaires d'héritabilité pour d'autres types de toxicomanie ont été indiqués par d'autres études.(39) Knestler a émis l'hypothèse en 1964 qu'un gène ou un groupe de gènes pourrait contribuer de plusieurs manières à la prédisposition à la dépendance. Par exemple, des niveaux modifiés d'une protéine normale dus à des facteurs environnementaux pourraient alors modifier la structure ou le fonctionnement de neurones cérébraux spécifiques au cours du développement. Ces neurones cérébraux modifiés pourraient modifier la sensibilité d'un individu à une première expérience de consommation de drogue. À l'appui de cette hypothèse, des études animales ont montré que des facteurs environnementaux tels que le stress peuvent affecter le génotype d'un animal.(39)

Dans l'ensemble, les données impliquant des gènes spécifiques dans le développement de la toxicomanie sont mitigées pour la plupart des gènes. L'une des raisons à cela peut être que le cas est dû à l'accent mis par les recherches actuelles sur les variantes courantes. De nombreuses études sur la toxicomanie se concentrent sur des variantes courantes avec une fréquence allélique supérieure à 5 % dans la population générale ; cependant, lorsqu'ils sont associés à la maladie, ceux-ci ne confèrent qu'une petite quantité de risque supplémentaire avec un rapport de cotes de 1,1 à 1,3 pour cent. D'autre part, l'hypothèse du variant rare affirme que les gènes à faible fréquence dans la population (<1%) confèrent un risque supplémentaire beaucoup plus important dans le développement de la maladie.(40)

Les études d'association pangénomique (GWAS) sont utilisées pour examiner les associations génétiques avec la dépendance, la toxicomanie et la consommation de drogues. Ces études utilisent une approche impartiale pour trouver des associations génétiques avec des phénotypes spécifiques et donnent un poids égal à toutes les régions de l'ADN, y compris celles qui n'ont aucune relation apparente avec le métabolisme ou la réponse aux médicaments. Ces études identifient rarement les gènes de protéines précédemment décrites via des modèles animaux knock-out et l'analyse des gènes candidats. Au lieu de cela, de grands pourcentages de gènes impliqués dans des processus tels que l'adhésion cellulaire sont couramment identifiés. Cela ne veut pas dire que les conclusions précédentes, ou les conclusions de GWAS, sont erronées. Les effets importants des endophénotypes ne peuvent généralement pas être capturés par ces méthodes. De plus, les gènes identifiés dans GWAS pour la toxicomanie peuvent être impliqués soit dans l'ajustement du comportement cérébral avant les expériences de drogue, après celles-ci, ou les deux.(41)

Une étude qui met en évidence le rôle important que joue la génétique dans la dépendance est les études jumelles. Les jumeaux ont une génétique similaire et parfois identique. L'analyse de ces gènes en relation avec la génétique a aidé les généticiens à comprendre à quel point les gènes jouent un rôle dans la dépendance. Des études réalisées sur des jumeaux ont révélé que rarement un seul jumeau avait une dépendance. Dans la plupart des cas où au moins un jumeau souffrait d'une dépendance, les deux en souffraient, et souvent à la même substance.(42) La dépendance croisée, c'est quand a déjà une dépendance prédisposée et commence alors à devenir accro à quelque chose de différent. Si un membre de la famille a des antécédents de toxicomanie, les chances qu'un parent ou une famille proche développe ces mêmes habitudes sont beaucoup plus élevées que celles qui n'ont pas été initiées à la toxicomanie à un jeune âge.(43) Dans une étude récente réalisée par le National Institute on Drug Abuse, de 2002 à 2017, les décès par surdose ont presque triplé chez les hommes et les femmes. En 2017, 72 306 décès par surdose ont été signalés aux États-Unis.(44) En 2020, les décès par surdose les plus élevés ont été enregistrés sur une période de 12 mois. Il y a eu 81 000 décès par surdose, dépassant de manière exponentielle les records de 2017.(45)

Facteurs environnementaux(Éditer)

Les facteurs de risque environnementaux d'addiction sont les expériences d'un individu au cours de sa vie qui interagissent avec la composition génétique de l'individu pour augmenter ou diminuer sa vulnérabilité à l'addiction.(3) Par exemple, après l'épidémie nationale de COVID-19, plus de personnes ont cessé (vs ont commencé) de fumer ; et les fumeurs, en moyenne, ont réduit la quantité de cigarettes qu'ils consommaient.(46) Plus généralement, un certain nombre de facteurs environnementaux différents ont été impliqués comme facteurs de risque de dépendance, y compris divers facteurs de stress psychosociaux. Le National Institute on Drug Abuse (NIDA) cite le manque de supervision parentale, la prévalence de la consommation de substances par les pairs, la disponibilité des drogues et la pauvreté comme facteurs de risque de consommation de substances chez les enfants et les adolescents.(47) Le modèle de maladie cérébrale de la toxicomanie postule que l'exposition d'un individu à une drogue addictive est le facteur de risque environnemental le plus important pour la toxicomanie.(48) Cependant, de nombreux chercheurs, y compris des neuroscientifiques, indiquent que le modèle de la maladie cérébrale présente une explication trompeuse, incomplète et potentiellement préjudiciable de la dépendance.(49)

Les expériences défavorables de l'enfance (ACE) sont diverses formes de maltraitance et de dysfonctionnement familial vécues pendant l'enfance. L'étude Adverse Childhood Experiences des Centers for Disease Control and Prevention a montré une forte relation dose-réponse entre les ECA et de nombreux problèmes de santé, sociaux et comportementaux tout au long de la vie d'une personne, y compris la toxicomanie.(50) Le développement neurologique des enfants peut être perturbé de façon permanente lorsqu'ils sont exposés de manière chronique à des événements stressants tels que des abus physiques, émotionnels ou sexuels, une négligence physique ou émotionnelle, des témoins de violence au sein du foyer ou un parent incarcéré ou souffrant d'une maladie mentale. En conséquence, le fonctionnement cognitif de l'enfant ou sa capacité à faire face à des émotions négatives ou perturbatrices peuvent être altérés. Au fil du temps, l'enfant peut adopter la consommation de substances comme mécanisme d'adaptation, en particulier pendant l'adolescence.(50) Une étude de 900 affaires judiciaires impliquant des enfants victimes de violence a révélé qu'un grand nombre d'entre eux ont souffert d'une forme de dépendance au cours de leur adolescence ou de leur vie adulte.(51) Cette voie vers la dépendance qui s'ouvre à travers des expériences stressantes pendant l'enfance peut être évitée par un changement des facteurs environnementaux tout au long de la vie d'un individu et des opportunités d'aide professionnelle.(51) Si l'on a des amis ou des pairs qui s'engagent favorablement dans la consommation de drogues, les chances qu'ils développent une dépendance augmentent. Les conflits familiaux et la gestion du foyer sont également une cause pour une personne de s'engager dans la consommation d'alcool ou d'autres drogues.(52)

Âge(Éditer)

L'adolescence représente une période de vulnérabilité unique pour développer une dépendance.(53) À l'adolescence, les systèmes d'incitation-récompense dans le cerveau mûrissent bien avant le centre de contrôle cognitif. Cela confère par conséquent aux systèmes d'incitation-récompenses un pouvoir disproportionné dans le processus de prise de décision comportementale. Par conséquent, les adolescents sont de plus en plus susceptibles d'agir selon leurs impulsions et de s'engager dans des comportements à risque et potentiellement addictifs avant d'envisager les conséquences.(54) Non seulement les adolescents sont plus susceptibles de commencer et de continuer à consommer de la drogue, mais une fois dépendants, ils sont plus résistants au traitement et plus susceptibles de rechuter.(55)(56)

Les statistiques ont montré que ceux qui commencent à boire de l'alcool à un plus jeune âge sont plus susceptibles de devenir dépendants plus tard. Environ 33 % de la population(où?) ont goûté leur premier alcool entre 15 et 17 ans, tandis que 18 % en ont déjà consommé. En ce qui concerne l'abus ou la dépendance à l'alcool, les chiffres commencent haut avec ceux qui ont d'abord bu avant l'âge de 12 ans, puis baissent ensuite. Par exemple, 16 % des alcooliques ont commencé à boire avant l'âge de 12 ans, tandis que seulement 9 % ont touché pour la première fois à l'alcool entre 15 et 17 ans. Ce pourcentage est encore plus faible, à 2,6 %, pour ceux qui ont commencé à consommer après 21 ans.(57)

La plupart des individus sont exposés à des drogues addictives et en consomment pour la première fois au cours de leur adolescence.(58) Aux États-Unis, il y avait un peu plus de 2,8 millions de nouveaux utilisateurs de drogues illicites en 2013 (environ 7 800 nouveaux utilisateurs par jour) ;(58) parmi eux, 54,1 % avaient moins de 18 ans.(58) En 2011, il y avait environ 20,6 millions de personnes aux États-Unis de plus de 12 ans souffrant d'une dépendance.(59) Plus de 90 % des toxicomanes ont commencé à boire, à fumer ou à consommer des drogues illicites avant l'âge de 18 ans.(59)

Troubles comorbides(Éditer)

Les personnes atteintes de troubles de santé mentale comorbides (c.-à-d. co-occurrents) tels que la dépression, l'anxiété, le trouble déficitaire de l'attention/hyperactivité (TDAH) ou le trouble de stress post-traumatique sont plus susceptibles de développer des troubles liés à l'utilisation de substances.(60)(61)(62) le NIDA cite un comportement agressif précoce comme facteur de risque de consommation de substances.(47) Une étude du National Bureau of Economic Research a révélé qu'il existe un « lien certain entre la maladie mentale et la consommation de substances addictives » et qu'une majorité de patients souffrant de troubles mentaux participent à la consommation de ces substances : 38 % d'alcool, 44 % de cocaïne, et 40 % de cigarettes.(63)

Épigénétique(Éditer)

Hérédité épigénétique transgénérationnelle(Éditer)

Les gènes épigénétiques et leurs produits (par exemple, les protéines) sont les éléments clés par lesquels les influences environnementales peuvent affecter les gènes d'un individu ;(37) ils servent également de mécanisme responsable de l'héritage épigénétique transgénérationnel, un phénomène dans lequel les influences environnementales sur les gènes d'un parent peuvent affecter les traits associés et les phénotypes comportementaux de leur progéniture (par exemple, les réponses comportementales aux stimuli environnementaux).(37) Dans l'addiction, les mécanismes épigénétiques jouent un rôle central dans la physiopathologie de la maladie ;(3) il a été noté que certaines des altérations de l'épigénome résultant d'une exposition chronique à des stimuli addictifs au cours d'une dépendance peuvent être transmises d'une génération à l'autre, affectant à leur tour le comportement des enfants (par exemple, les réponses comportementales de l'enfant aux drogues addictives et aux récompenses naturelles ).(37)(64)

Les classes générales d'altérations épigénétiques qui ont été impliquées dans l'héritage épigénétique transgénérationnel comprennent la méthylation de l'ADN, les modifications des histones et la régulation négative ou positive des microARN.(37) En ce qui concerne la dépendance, des recherches supplémentaires sont nécessaires pour déterminer les altérations épigénétiques héréditaires spécifiques qui découlent de diverses formes de dépendance chez l'homme et les phénotypes comportementaux correspondants de ces altérations épigénétiques qui se produisent chez la progéniture humaine.(37)(64) Sur la base des preuves précliniques de la recherche animale, certaines altérations épigénétiques induites par la dépendance chez le rat peuvent être transmises du parent à la progéniture et produire des phénotypes comportementaux qui diminuent le risque de développer une dépendance chez la progéniture.(note 2)(37) Plus généralement, les phénotypes comportementaux héréditaires dérivés d'altérations épigénétiques induites par la dépendance et transmis des parents à la progéniture peuvent servir à augmenter ou à diminuer le risque de développer une dépendance chez la progéniture.(37)(64)

Responsabilité en cas d'abus

La responsabilité en cas d'abus, également connue sous le nom de responsabilité en matière de toxicomanie, est la propension à consommer des drogues dans une situation non médicale. C'est généralement pour l'euphorie, le changement d'humeur ou la sédation.(65) La responsabilité en cas d'abus est utilisée lorsque la personne qui utilise la drogue veut quelque chose qu'elle ne pourrait pas obtenir autrement. La seule façon d'y parvenir est de consommer des drogues. Lorsqu'on examine la responsabilité en cas d'abus, il existe un certain nombre de facteurs déterminants pour déterminer si la drogue est maltraitée. Ces facteurs sont : la composition chimique du médicament, les effets sur le cerveau, et l'âge, la vulnérabilité et la santé (mentale et physique) de la population étudiée.(65) Il existe quelques médicaments avec une composition chimique spécifique qui entraîne un risque élevé d'abus. Ce sont : la cocaïne, l'héroïne, les substances inhalées, le LSD, la marijuana, la MDMA (ecstasy), la méthamphétamine, le PCP, les cannabinoïdes synthétiques, les cathinones synthétiques (sels de bain), le tabac et l'alcool.(66)

Mécanismes(Éditer)

Glossaire des facteurs de transcription
  • l'expression du gène – le processus par lequel l'information d'un gène est utilisée dans la synthèse d'un produit génique fonctionnel tel qu'une protéine
  • transcription – le processus de fabrication d'ARN messager (ARNm) à partir d'une matrice d'ADN par l'ARN polymérase
  • le facteur de transcription – une protéine qui se lie à l'ADN et régule l'expression des gènes en favorisant ou en supprimant la transcription
  • régulation transcriptionnellecontrôler le taux de transcription des gènes, par exemple en aidant ou en empêchant la liaison de l'ARN polymérase à l'ADN
  • régulation à la hausse, Activation, ou alors promotionaugmenter le taux de transcription des gènes
  • régulation à la baisse, répression, ou alors suppressiondiminuer le taux de transcription des gènes
  • coactivateur – une protéine (ou une petite molécule) qui travaille avec des facteurs de transcription pour augmenter le taux de transcription des gènes
  • corépresseur – une protéine (ou une petite molécule) qui travaille avec des facteurs de transcription pour diminuer le taux de transcription des gènes
  • élément de réponse – une séquence spécifique d’ADN à laquelle se lie un facteur de transcription
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Ce diagramme illustre les événements de signalisation dans le centre de récompense du cerveau qui sont induits par une exposition chronique à forte dose à des psychostimulants qui augmentent la concentration de dopamine synaptique, comme l'amphétamine, la méthamphétamine et la phénéthylamine. Suite à la co-libération présynaptique de dopamine et de glutamate par ces psychostimulants,(67)(68) les récepteurs postsynaptiques de ces neurotransmetteurs déclenchent des événements de signalisation internes via une voie dépendante de l'AMPc et une voie dépendante du calcium qui entraînent finalement une augmentation CREB phosphorylation.(67)(69)(70) Le CREB phosphorylé augmente les niveaux de ΔFosB, qui à son tour réprime le c-Fos gène à l'aide de corépresseurs;(67)(71)(72) c-Fos la répression agit comme un interrupteur moléculaire qui permet l'accumulation de ΔFosB dans le neurone.(73) Une forme hautement stable (phosphorylée) de ΔFosB, qui persiste dans les neurones pendant 1-2 mois, s'accumule lentement à la suite d'expositions répétées à des doses élevées de stimulants par le biais de ce processus.(71)(72) ΔFosB fonctionne comme "l'une des protéines de contrôle principales" qui produit des changements structurels liés à la dépendance dans le cerveau, et lors d'une accumulation suffisante, avec l'aide de ses cibles en aval (par exemple, le facteur nucléaire kappa B), il induit un état de dépendance.(71)(72)

La toxicomanie chronique provoque des altérations de l'expression des gènes dans la projection mésocorticolimbique.(18)(74)(75) Les facteurs de transcription les plus importants qui produisent ces altérations sont ΔFosB, la protéine de liaison à l'élément de réponse à l'AMPc (CREB) et le facteur nucléaire kappa B (NF-κB).(18) ΔFosB est le mécanisme biomoléculaire le plus important dans la toxicomanie, car la surexpression de ΔFosB dans les neurones épineux moyens de type D1 du noyau accumbens est nécessaire et suffisante pour de nombreuses adaptations neurales et effets comportementaux (par exemple, augmentations dépendantes de l'expression de l'auto-médicament). l'administration et la sensibilisation à la récompense) observées dans la toxicomanie.(18) L'expression ΔFosB dans les neurones épineux moyens de type D1 du noyau accumbens régule directement et positivement l'auto-administration du médicament et la sensibilisation à la récompense par le renforcement positif tout en diminuant la sensibilité à l'aversion.(note 1)(3)(15) ΔFosB a été impliqué dans la médiation des dépendances à de nombreuses drogues et classes de drogues différentes, notamment l'alcool, les amphétamines et d'autres amphétamines substituées, les cannabinoïdes, la cocaïne, le méthylphénidate, la nicotine, les opiacés, la phénylcyclidine et le propofol, entre autres.(15)(18)(74)(76)(77) ΔJunD, un facteur de transcription, et G9a, une histone méthyltransférase, s'opposent tous deux à la fonction de ΔFosB et inhibent l'augmentation de son expression.(3)(18)(78) L'augmentation de l'expression du noyau accumbens Δ JunD (via le transfert de gènes à médiation virale) ou l'expression de G9a (via des moyens pharmacologiques) réduit, ou avec une forte augmentation peut même bloquer, de nombreuses altérations neurales et comportementales qui résultent de l'utilisation chronique de fortes doses de drogues addictives (c'est-à-dire les altérations médiées par ΔFosB).(17)(18)

ΔFosB joue également un rôle important dans la régulation des réponses comportementales aux récompenses naturelles, telles que la nourriture agréable au goût, le sexe et l'exercice.(18)(79) Les récompenses naturelles, comme les drogues d'abus, induisent l'expression génique de FosB dans le noyau accumbens, et l'acquisition chronique de ces récompenses peut entraîner un état de dépendance pathologique similaire via la surexpression de ΔFosB.(16)(18)(79) Par conséquent, ΔFosB est également le facteur de transcription clé impliqué dans les dépendances aux récompenses naturelles (c'est-à-dire les dépendances comportementales);(18)(16)(79) en particulier, ΔFosB dans le noyau accumbens est essentiel pour les effets de renforcement de la récompense sexuelle.(79) Les recherches sur l'interaction entre les récompenses naturelles et médicamenteuses suggèrent que les psychostimulants dopaminergiques (par exemple, les amphétamines) et le comportement sexuel agissent sur des mécanismes biomoléculaires similaires pour induire ΔFosB dans le noyau accumbens et possèdent des effets de sensibilisation croisée bidirectionnels qui sont médiés par ΔFosB.(16)(32)(33) Ce phénomène est notable puisque, chez l'homme, un syndrome de dérégulation de la dopamine, caractérisé par un engagement compulsif induit par les médicaments dans des récompenses naturelles (en particulier, l'activité sexuelle, les achats et le jeu), a également été observé chez certaines personnes prenant des médicaments dopaminergiques.(16)

Les inhibiteurs de FosB (médicaments ou traitements qui s'opposent à son action) peuvent être un traitement efficace de l'addiction et des troubles addictifs.(80)

La libération de dopamine dans le noyau accumbens joue un rôle dans les qualités de renforcement de nombreuses formes de stimuli, y compris les stimuli naturellement renforçants comme la nourriture agréable au goût et le sexe.(81)(82) Une altération de la neurotransmission de la dopamine est fréquemment observée suite au développement d'un état addictif.(16) Chez les humains et les animaux de laboratoire qui ont développé une dépendance, des altérations de la neurotransmission de la dopamine ou des opioïdes dans le noyau accumbens et d'autres parties du striatum sont évidentes.(16) Des études ont montré que l'utilisation de certaines drogues (par exemple, la cocaïne) affecte les neurones cholinergiques qui innervent le système de récompense, affectant à son tour la signalisation de la dopamine dans cette région.(83)

Système de récompense(Éditer)

Voie mésocorticolimbique(Éditer)

Comprendre les voies dans lesquelles les drogues agissent et comment les drogues peuvent modifier ces voies est essentiel lors de l'examen des bases biologiques de la toxicomanie. La voie de récompense, connue sous le nom de voie mésolimbique, ou son extension, la voie mésocorticolimbique, est caractérisée par l'interaction de plusieurs zones du cerveau.

  • Les projections de l'aire tegmentale ventrale (VTA) sont un réseau de neurones dopaminergiques avec des récepteurs post-synaptiques du glutamate co-localisés (AMPAR et NMDAR). Ces cellules réagissent lorsque des stimuli indiquant une récompense sont présents. Le VTA prend en charge le développement de l'apprentissage et de la sensibilisation et libère le DA dans le cerveau antérieur.(85) Ces neurones projettent et libèrent également du DA dans le noyau accumbens,(86) par la voie mésolimbique. Pratiquement tous les médicaments provoquant une toxicomanie augmentent la libération de dopamine dans la voie mésolimbique,(87) en plus de leurs effets spécifiques.
  • Le noyau accumbens (NAcc) est une sortie des projections VTA. Le noyau accumbens lui-même se compose principalement de neurones épineux moyens (MSN) GABAergiques.(88) Le NAcc est associé à l'acquisition et au déclenchement de comportements conditionnés, et est impliqué dans l'augmentation de la sensibilité aux drogues à mesure que la dépendance progresse.(85) La surexpression de ΔFosB dans le noyau accumbens est un facteur commun nécessaire dans pratiquement toutes les formes connues de dépendance;(3) ΔFosB est un puissant modulateur positif de comportements positivement renforcés.(3)
  • Le cortex préfrontal, y compris les cortex cingulaire antérieur et orbitofrontal,(89) est une autre sortie de VTA dans la voie mésocorticolimbique ; il est important pour l'intégration des informations qui aident à déterminer si un comportement sera suscité.(90) Il est également essentiel pour former des associations entre l'expérience enrichissante de l'usage de drogues et les signaux dans l'environnement. Il est important de noter que ces signaux sont de puissants médiateurs du comportement de recherche de drogue et peuvent déclencher une rechute même après des mois ou des années d'abstinence.(91)

Les autres structures cérébrales impliquées dans la toxicomanie comprennent :

  • L'amygdale basolatérale se projette dans la NAcc et est également considérée comme importante pour la motivation.(90)
  • L'hippocampe est impliqué dans la toxicomanie, en raison de son rôle dans l'apprentissage et la mémoire. Une grande partie de ces preuves provient d'enquêtes montrant que la manipulation des cellules de l'hippocampe modifie les niveaux de dopamine dans la NAcc et les taux de décharge des cellules dopaminergiques VTA.(86)

Rôle de la dopamine et du glutamate(Éditer)

La dopamine est le principal neurotransmetteur du système de récompense dans le cerveau. Il joue un rôle dans la régulation du mouvement, des émotions, de la cognition, de la motivation et des sensations de plaisir.(92) Les récompenses naturelles, comme manger, ainsi que la consommation de drogues récréatives provoquent une libération de dopamine et sont associées à la nature renforçante de ces stimuli.(92)(93) Presque toutes les drogues provoquant une dépendance, directement ou indirectement, agissent sur le système de récompense du cerveau en augmentant l'activité dopaminergique.(94)

Une consommation excessive de nombreux types de drogues provoquant une dépendance entraîne une libération répétée de grandes quantités de dopamine, qui à son tour affecte la voie de la récompense directement par l'activation accrue des récepteurs de la dopamine. Des niveaux prolongés et anormalement élevés de dopamine dans la fente synaptique peuvent induire une régulation négative des récepteurs dans la voie neurale. La régulation à la baisse des récepteurs mésolimbiques de la dopamine peut entraîner une diminution de la sensibilité aux renforçateurs naturels.(92)

Drug seeking behavior is induced by glutamatergic projections from the prefrontal cortex to the nucleus accumbens. This idea is supported with data from experiments showing that drug seeking behavior can be prevented following the inhibition of AMPA glutamate receptors and glutamate release in the nucleus accumbens.(89)

Reward sensitization(Éditer)

Neural and behavioral effects of validated ΔFosB transcriptional targets in the striatum(15)(95)
Cible
gene
Cible
expression
Neural effectsBehavioral effects
c-FosMolecular switch enabling the chronic
induction of ΔFosB(note 3)
dynorphin
(note 4)
• Downregulation of κ-opioid feedback loop • Increased drug reward
NF-κB • Expansion of NAcc dendritic processes
• NF-κB inflammatory response in the NAcc
• NF-κB inflammatory response in the CP
• Increased drug reward
• Increased drug reward
• Locomotor sensitization
GluR2 • Decreased sensitivity to glutamate • Increased drug reward
Cdk5 • GluR1 synaptic protein phosphorylation
• Expansion of NAcc dendritic processes
Decreased drug reward
(net effect)

Reward sensitization is a process that causes an increase in the amount of reward (specifically, incentive salience(note 5)) that is assigned by the brain to a rewarding stimulus (e.g., a drug). In simple terms, when reward sensitization to a specific stimulus (e.g., a drug) occurs, an individual's "wanting" or desire for the stimulus itself and its associated cues increases.(97)(96)(98) Reward sensitization normally occurs following chronically high levels of exposure to the stimulus. ΔFosB (DeltaFosB) expression in D1-type medium spiny neurons in the nucleus accumbens has been shown to directly and positively regulate reward sensitization involving drugs and natural rewards.(3)(15)(17)

"Cue-induced wanting" or "cue-triggered wanting", a form of craving that occurs in addiction, is responsible for most of the compulsive behavior that addicts exhibit.(96)(98) During the development of an addiction, the repeated association of otherwise neutral and even non-rewarding stimuli with drug consumption triggers an associative learning process that causes these previously neutral stimuli to act as conditioned positive reinforcers of addictive drug use (i.e., these stimuli start to function as drug cues).(96)(99)(98) As conditioned positive reinforcers of drug use, these previously neutral stimuli are assigned incentive salience (which manifests as a craving) – sometimes at pathologically high levels due to reward sensitization – which can transfer to the primary reinforcer (e.g., the use of an addictive drug) with which it was originally paired.(96)(99)(98)

Research on the interaction between natural and drug rewards suggests that dopaminergic psychostimulants (e.g., amphetamine) and sexual behavior act on similar biomolecular mechanisms to induce ΔFosB in the nucleus accumbens and possess a bidirectional reward cross-sensitization effect(note 6) that is mediated through ΔFosB.(16)(32)(33) In contrast to ΔFosB's reward-sensitizing effect, CREB transcriptional activity decreases user's sensitivity to the rewarding effects of the substance. CREB transcription in the nucleus accumbens is implicated in psychological dependence and symptoms involving a lack of pleasure or motivation during drug withdrawal.(3)(84)(95)

The set of proteins known as "regulators of G protein signaling" (RGS), particularly RGS4 and RGS9-2, have been implicated in modulating some forms of opioid sensitization, including reward sensitization.(100)

Neuroepigenetic mechanisms(Éditer)

Altered epigenetic regulation of gene expression within the brain's reward system plays a significant and complex role in the development of drug addiction.(78)(101) Addictive drugs are associated with three types of epigenetic modifications within neurons.(78) These are (1) histone modifications, (2) epigenetic methylation of DNA at CpG sites at (or adjacent to) particular genes, and (3) epigenetic downregulation or upregulation of microRNAs which have particular target genes.(78)(18)(101) As an example, while hundreds of genes in the cells of the nucleus accumbens (NAc) exhibit histone modifications following drug exposure – particularly, altered acetylation and methylation states of histone residues(101) – most other genes in the NAc cells do not show such changes.(78)

Diagnosis(Éditer)

The 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) uses the term "substance use disorder" to refer to a spectrum of drug use-related disorders. The DSM-5 eliminates the terms "abuse" and "dependence" from diagnostic categories, instead using the specifiers of mild, moderate et severe to indicate the extent of disordered use. These specifiers are determined by the number of diagnostic criteria present in a given case. In the DSM-5, the term drug addiction is synonymous with severe substance use disorder.(1)(2)

The DSM-5 introduced a new diagnostic category for behavioral addictions; however, problem gambling is the only condition included in that category in the 5th edition.(26) Internet gaming disorder is listed as a "condition requiring further study" in the DSM-5.(102)

Past editions have used physical dependence and the associated withdrawal syndrome to identify an addictive state. Physical dependence occurs when the body has adjusted by incorporating the substance into its "normal" functioning – i.e., attains homeostasis – and therefore physical withdrawal symptoms occur upon cessation of use.(103) Tolerance is the process by which the body continually adapts to the substance and requires increasingly larger amounts to achieve the original effects. Withdrawal refers to physical and psychological symptoms experienced when reducing or discontinuing a substance that the body has become dependent on. Symptoms of withdrawal generally include but are not limited to body aches, anxiety, irritability, intense cravings for the substance, nausea, hallucinations, headaches, cold sweats, tremors, and seizures.

Medical researchers who actively study addiction have criticized the DSM classification of addiction for being flawed and involving arbitrary diagnostic criteria.(27) Writing in 2013, the director of the United States National Institute of Mental Health discussed the invalidity of the DSM-5's classification of mental disorders:(104)

While DSM has been described as a "Bible" for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been "reliability" – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. In the rest of medicine, this would be equivalent to creating diagnostic systems based on the nature of chest pain or the quality of fever.

Given that addiction manifests in structural changes to the brain, it is possible that non-invasive neuroimaging scans obtained via MRI could be used to help diagnose addiction in the future.(105) As a diagnostic biomarker, ΔFosB expression could be used to diagnose an addiction in humans, but this would require a brain biopsy and therefore is not used in clinical practice.

Traitement(Éditer)

According to a review, "in order to be effective, all pharmacological or biologically based treatments for addiction need to be integrated into other established forms of addiction rehabilitation, such as cognitive behavioral therapy, individual and group psychotherapy, behavior modification strategies, twelve-step programs, and residential treatment facilities."(8)

Behavioral therapy(Éditer)

A meta-analytic review on the efficacy of various behavioral therapies for treating drug and behavioral addictions found that cognitive behavioral therapy (e.g., relapse prevention and contingency management), motivational interviewing, and a community reinforcement approach were effective interventions with moderate effect sizes.(106)

Clinical and preclinical evidence indicate that consistent aerobic exercise, especially endurance exercise (e.g., marathon running), actually prevents the development of certain drug addictions and is an effective adjunct treatment for drug addiction, and for psychostimulant addiction in particular.(16)(107)(108)(109)(110) Consistent aerobic exercise magnitude-dependently (i.e., by duration and intensity) reduces drug addiction risk, which appears to occur through the reversal of drug induced addiction-related neuroplasticity.(16)(108) One review noted that exercise may prevent the development of drug addiction by altering ΔFosB or c-Fos immunoreactivity in the striatum or other parts of the reward system.(110) Aerobic exercise decreases drug self-administration, reduces the likelihood of relapse, and induces opposite effects on striatal dopamine receptor D2 (DRD2) signaling (increased DRD2 density) to those induced by addictions to several drug classes (decreased DRD2 density).(16)(108) Consequently, consistent aerobic exercise may lead to better treatment outcomes when used as an adjunct treatment for drug addiction.(16)(108)(109)

Des médicaments(Éditer)

Alcohol addiction(Éditer)

Alcohol, like opioids, can induce a severe state of physical dependence and produce withdrawal symptoms such as delirium tremens. Because of this, treatment for alcohol addiction usually involves a combined approach dealing with dependence and addiction simultaneously. Benzodiazepines have the largest and the best evidence base in the treatment of alcohol withdrawal and are considered the gold standard of alcohol detoxification.(111)

Pharmacological treatments for alcohol addiction include drugs like naltrexone (opioid antagonist), disulfiram, acamprosate, and topiramate.(112)(113) Rather than substituting for alcohol, these drugs are intended to affect the desire to drink, either by directly reducing cravings as with acamprosate and topiramate, or by producing unpleasant effects when alcohol is consumed, as with disulfiram. These drugs can be effective if treatment is maintained, but compliance can be an issue as alcoholic patients often forget to take their medication, or discontinue use because of excessive side effects.(114)(115) According to a Cochrane Collaboration review, the opioid antagonist naltrexone has been shown to be an effective treatment for alcoholism, with the effects lasting three to twelve months after the end of treatment.(116)

Behavioral addictions(Éditer)

Behavioral addiction is a treatable condition. Treatment options include psychotherapy and psychopharmacotherapy (i.e., medications) or a combination of both. Cognitive behavioral therapy (CBT) is the most common form of psychotherapy used in treating behavioral addictions; it focuses on identifying patterns that trigger compulsive behavior and making lifestyle changes to promote healthier behaviors. Because cognitive behavioral therapy is considered a short term therapy, the number of sessions for treatment normally ranges from five to twenty. During the session, therapists will lead patients through the topics of identifying the issue, becoming aware of one's thoughts surrounding the issue, identifying any negative or false thinking, and reshaping said negative and false thinking. While CBT does not cure behavioral addiction, it does help with coping with the condition in a healthy way. Currently, there are no medications approved for treatment of behavioral addictions in general, but some medications used for treatment of drug addiction may also be beneficial with specific behavioral addictions.(36)(117) Any unrelated psychiatric disorders should be kept under control, and differentiated from the contributing factors that cause the addiction.

Cannabinoid addiction(Éditer)

As of 2010, there are no effective pharmacological interventions for cannabinoid addiction.(118) A 2013 review on cannabinoid addiction noted that the development of CB1 receptor agonists that have reduced interaction with β-arrestin 2 signaling might be therapeutically useful.(119)

Nicotine addiction(Éditer)

Another area in which drug treatment has been widely used is in the treatment of nicotine addiction, which usually involves the use of nicotine replacement therapy, nicotinic receptor antagonists, or nicotinic receptor partial agonists.(120)(121) Examples of drugs that act on nicotinic receptors and have been used for treating nicotine addiction include antagonists like bupropion and the partial agonist varenicline.(120)(121)

Opioid addiction(Éditer)

Opioids cause physical dependence, and treatment typically addresses both dependence and addiction.

Physical dependence is treated using replacement drugs such as suboxone or subutex (both containing the active ingredients buprenorphine) and methadone.(122)(123) Although these drugs perpetuate physical dependence, the goal of opiate maintenance is to provide a measure of control over both pain and cravings. Use of replacement drugs increases the addicted individual's ability to function normally and eliminates the negative consequences of obtaining controlled substances illicitly. Once a prescribed dosage is stabilized, treatment enters maintenance or tapering phases. In the United States, opiate replacement therapy is tightly regulated in methadone clinics and under the DATA 2000 legislation. In some countries, other opioid derivatives such as dihydrocodeine,(124) dihydroetorphine(125) and even heroin(126)(127) are used as substitute drugs for illegal street opiates, with different prescriptions being given depending on the needs of the individual patient. Baclofen has led to successful reductions of cravings for stimulants, alcohol, and opioids, and also alleviates alcohol withdrawal syndrome. Many patients have stated they "became indifferent to alcohol" or "indifferent to cocaine" overnight after starting baclofen therapy.(128) Some studies show the interconnection between opioid drug detoxification and overdose mortality.(129)

Psychostimulant addiction(Éditer)

As of May 2014, there is no effective pharmacotherapy for any form of psychostimulant addiction.(8)(130)(131)(132) Reviews from 2015, 2016, and 2018 indicated that TAAR1-selective agonists have significant therapeutic potential as a treatment for psychostimulant addictions;(133)(134)(135) however, as of 2018, the only compounds which are known to function as TAAR1-selective agonists are experimental drugs.(133)(134)(135)

Recherche(Éditer)

Research indicates that vaccines which utilize anti-drug monoclonal antibodies can mitigate drug-induced positive reinforcement by preventing the drug from moving across the blood–brain barrier;(136) however, current vaccine-based therapies are only effective in a relatively small subset of individuals.(136)(137) As of November 2015, vaccine-based therapies are being tested in human clinical trials as a treatment for addiction and preventive measure against drug overdoses involving nicotine, cocaine, and methamphetamine.(136)

The new study shows, that the vaccine may also save lives during a drug overdose. In this instance, the idea is that the body will respond to the vaccine by quickly producing antibodies to prevent the opioids from accessing the brain.(138)

Since addiction involves abnormalities in glutamate and GABAergic neurotransmission,(139)(140) receptors associated with these neurotransmitters (e.g., AMPA receptors, NMDA receptors, and GABAB receptors) are potential therapeutic targets for addictions.(139)(140)(141)(142) N-acetylcysteine, which affects metabotropic glutamate receptors and NMDA receptors, has shown some benefit in preclinical and clinical studies involving addictions to cocaine, heroin, and cannabinoids.(139) It may also be useful as an adjunct therapy for addictions to amphetamine-type stimulants, but more clinical research is required.(139)

Current medical reviews of research involving lab animals have identified a drug class – class I histone deacetylase inhibitors(note 7) – that indirectly inhibits the function and further increases in the expression of accumbal ΔFosB by inducing G9a expression in the nucleus accumbens after prolonged use.(17)(78)(143)(101) These reviews and subsequent preliminary evidence which used oral administration or intraperitoneal administration of the sodium salt of butyric acid or other class I HDAC inhibitors for an extended period indicate that these drugs have efficacy in reducing addictive behavior in lab animals(note 8) that have developed addictions to ethanol, psychostimulants (i.e., amphetamine and cocaine), nicotine, and opiates;(78)(101)(144)(145) however, few clinical trials involving human addicts and any HDAC class I inhibitors have been conducted to test for treatment efficacy in humans or identify an optimal dosing regimen.(note 9)

Gene therapy for addiction is an active area of research. One line of gene therapy research involves the use of viral vectors to increase the expression of dopamine D2 receptor proteins in the brain.(147)(148)(149)(150)(151)

Epidemiology(Éditer)

Due to cultural variations, the proportion of individuals who develop a drug or behavioral addiction within a specified time period (i.e., the prevalence) varies over time, by country, and across national population demographics (e.g., by age group, socioeconomic status, etc.).(37)

Asie(Éditer)

The prevalence of alcohol dependence is not as high as is seen in other regions. In Asia, not only socioeconomic factors but also biological factors influence drinking behavior.(152)

The overall prevalence of smartphone ownership is 62%, ranging from 41% in China to 84% in South Korea. Moreover, participation in online gaming ranges from 11% in China to 39% in Japan. Hong Kong has the highest number of adolescents reporting daily or above Internet use (68%). Internet addiction disorder is highest in the Philippines, according to both the IAT (Internet Addiction Test) – 5% and the CIAS-R (Revised Chen Internet Addiction Scale) – 21%.(153)

Australie(Éditer)

The prevalence of substance abuse disorder among Australians was reported at 5.1% in 2009.(154)

L'Europe (Éditer)

In 2015, the estimated prevalence among the adult population was 18.4% for heavy episodic alcohol use (in the past 30 days); 15.2% for daily tobacco smoking; and 3.8, 0.77, 0.37 and 0.35% in 2017 cannabis, amphetamine, opioid and cocaine use. The mortality rates for alcohol and illicit drugs were highest in Eastern Europe.(155)

United States(Éditer)

Based upon representative samples of the US youth population in 2011, the lifetime prevalence(note 10) of addictions to alcohol and illicit drugs has been estimated to be approximately 8% and 2–3% respectively.(20) Based upon representative samples of the US adult population in 2011, the 12 month prevalence of alcohol and illicit drug addictions were estimated at roughly 12% and 2–3% respectively.(20) The lifetime prevalence of prescription drug addictions is currently around 4.7%.(156)

As of 2016, about 22 million people in the United States need treatment for an addiction to alcohol, nicotine, or other drugs.(21)(157) Only about 10%, or a little over 2 million, receive any form of treatments, and those that do generally do not receive evidence-based care.(21)(157) One-third of inpatient hospital costs and 20% of all deaths in the US every year are the result of untreated addictions and risky substance use.(21)(157) In spite of the massive overall economic cost to society, which is greater than the cost of diabetes and all forms of cancer combined, most doctors in the US lack the training to effectively address a drug addiction.(21)(157)

Another review listed estimates of lifetime prevalence rates for several behavioral addictions in the United States, including 1–2% for compulsive gambling, 5% for sexual addiction, 2.8% for food addiction, and 5–6% for compulsive shopping.(16) A systematic review indicated that the time-invariant prevalence rate for sexual addiction and related compulsive sexual behavior (e.g., compulsive masturbation with or without pornography, compulsive cybersex, etc.) within the United States ranges from 3–6% of the population.(31)

According to a 2017 poll conducted by the Pew Research Center, almost half of US adults know a family member or close friend who has struggled with a drug addiction at some point in their life.(158)

In 2019, opioid addiction was acknowledged as a national crisis in the United States.(159) An article in Le Washington Post stated that "America’s largest drug companies flooded the country with pain pills from 2006 through 2012, even when it became apparent that they were fueling addiction and overdoses."

Amérique du Sud(Éditer)

The realities of opioid use and abuse in Latin America may be deceptive if observations are limited to epidemiological findings. In the United Nations Office on Drugs and Crime report,(160) although South America produced 3% of the world's morphine and heroin and 0.01% of its opium, prevalence of use is uneven. According to the Inter-American Commission on Drug Abuse Control, consumption of heroin is low in most Latin American countries, although Colombia is the area's largest opium producer. Mexico, because of its border with the United States, has the highest incidence of use.(161)

Personality theories(Éditer)

Personality theories of addiction are psychological models that associate personality traits or modes of thinking (i.e., affective states) with an individual's proclivity for developing an addiction. Data analysis demonstrates that there is a significant difference in the psychological profiles of drug users and non-users and the psychological predisposition to using different drugs may be different.(162) Models of addiction risk that have been proposed in psychology literature include an affect dysregulation model of positive and negative psychological affects, the reinforcement sensitivity theory model of impulsiveness and behavioral inhibition, and an impulsivity model of reward sensitization and impulsiveness.(163)(164)(165)(166)(167)

The suffixes "-holic" and "-holism"(Éditer)

In contemporary modern English "-holic" is a suffix that can be added to a subject to denote an addiction to it. It was extracted from the word alcoholism (one of the first addictions to be widely identified both medically and socially) (correctly the root "wikt:alcohol" plus the suffix "-ism") by misdividing or rebracketing it into "alco" and "-holism". (Another such misdivision is interpreting "helicopter" as "heli-copter" rather than the etymologically correct "helico-pter", giving rise to such derived words as "heliport" and "jetcopter".(168)) There are correct medico-legal terms for such addictions: dipsomania is the medico-legal term for alcoholism;(169) other examples are in this table:

The term "-holism" is not an accepted medical term, but is a fairly prominent neologism. As such, despite its widespread usage, it lacks a formal definition. The term can be used in many ways ranging from describing a physical or psychological dependency to something (ex. sexaholism(170)(171)), to a tendency to do something obsessively (ex. workaholism,(172) shopaholism(173)). "-Holism" can also be used by someone to express a strong passion for or interest in something. For example, professional wrestler Chris Jericho would refer to his fans as Jerichoholics.(174)

Voir également(Éditer)

  1. ^ une b A decrease in aversion sensitivity, in simpler terms, means that an individual's behavior is less likely to be influenced by undesirable outcomes.
  2. ^ According to a review of experimental animal models that examined the transgenerational epigenetic inheritance of epigenetic marks that occur in addiction, alterations in histone acetylation – specifically, di-acetylation of lysine residues 9 and 14 on histone 3 (i.e., H3K9ac2 and H3K14ac2) in association with BDNF gene promoters – have been shown to occur within the medial prefrontal cortex (mPFC), testes, and sperm of cocaine-addicted male rats.(37) These epigenetic alterations in the rat mPFC result in increased BDNF gene expression within the mPFC, which in turn blunts the rewarding properties of cocaine and reduces cocaine self-administration.(37) The male but not female offspring of these cocaine-exposed rats inherited both epigenetic marks (i.e., di-acetylation of lysine residues 9 and 14 on histone 3) within mPFC neurons, the corresponding increase in BDNF expression within mPFC neurons, and the behavioral phenotype associated with these effects (i.e., a reduction in cocaine reward, resulting in reduced cocaine-seeking by these male offspring).(37) Consequently, the transmission of these two cocaine-induced epigenetic alterations (i.e., H3K9ac2 and H3K14ac2) in rats from male fathers to male offspring served to reduce the offspring's risk of developing an addiction to cocaine.(37) As of 2018, neither the heritability of these epigenetic marks in humans nor the behavioral effects of the marks within human mPFC neurons has been established.(37)
  3. ^ In other words, c-Fos repression allows ΔFosB to more rapidly accumulate within the D1-type medium spiny neurons of the nucleus accumbens because it is selectively induced in this state.(3) Prior to c-Fos repression, all Fos family proteins (e.g., c-Fos, Fra1, Fra2, FosB, and ΔFosB) are induced together, with ΔFosB expression increasing to a lesser extent.(3)
  4. ^ According to two medical reviews, ΔFosB has been implicated in causing both increases and decreases in dynorphin expression in different studies;(15)(95) this table entry reflects only a decrease.
  5. ^ Incentive salience, the "motivational salience" for a reward, is a "desire" or "want" attribute, which includes a motivational component, that the brain assigns to a rewarding stimulus.(96)(97) As a consequence, incentive salience acts as a motivational "magnet" for a rewarding stimulus that commands attention, induces approach, and causes the rewarding stimulus to be sought out.(96)
  6. ^ In simplest terms, this means that when either amphetamine or sex is perceived as more alluring or desirable through reward sensitization, this effect occurs with the other as well.
  7. ^ Inhibitors of class I histone deacetylase (HDAC) enzymes are drugs that inhibit four specific histone-modifying enzymes: HDAC1, HDAC2, HDAC3, and HDAC8. Most of the animal research with HDAC inhibitors has been conducted with four drugs: butyrate salts (mainly sodium butyrate), trichostatin A, valproic acid, and SAHA;(143)(101) butyric acid is a naturally occurring short-chain fatty acid in humans, while the latter two compounds are FDA-approved drugs with medical indications unrelated to addiction.
  8. ^ Specifically, prolonged administration of a class I HDAC inhibitor appears to reduce an animal's motivation to acquire and use an addictive drug without affecting an animals motivation to attain other rewards (i.e., it does not appear to cause motivational anhedonia) and reduce the amount of the drug that is self-administered when it is readily available.(78)(101)(144)
  9. ^ Among the few clinical trials that employed a class I HDAC inhibitor, one utilized valproate for methamphetamine addiction.(146)
  10. ^ The lifetime prevalence of an addiction is the percentage of individuals in a population that developed an addiction at some point in their life.
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Les références(Éditer)

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    Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification of severe substance-use disorder.
  3. ^ une b c e F g h je j k l m m o p q r s t vous Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues in Clinical Neuroscience. 15 (4): 431–443. PMC 3898681. PMID 24459410. Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. … A large body of literature has demonstrated that such ΔFosB induction in D1-type (nucleus accumbens) neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement … Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41 … Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.
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  7. ^ une b Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 364–65, 375. ISBN 978-0-07-148127-4. The defining feature of addiction is compulsive, out-of-control drug use, despite negative consequences. …
    compulsive eating, shopping, gambling, and sex – so-called "natural addictions" – Indeed, addiction to both drugs and behavioral rewards may arise from similar dysregulation of the mesolimbic dopamine system.
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  14. ^ Henden E (2017). "Addiction, Compulsion, and Weakness of the Will: A Dual-Process Perspective.". In Heather N, Gabriel S (eds.). Addiction and Choice: Rethinking the Relationship. Oxford, UK: Oxford University Press. pp. 116–132.
  15. ^ une b c e F g h je j Ruffle JK (November 2014). "Molecular neurobiology of addiction: what's all the (Δ)FosB about?". Un m. J. Drug Alcohol Abuse. 40 (6): 428–37. doi:10.3109/00952990.2014.933840. PMID 25083822. S2CID 19157711.
    The strong correlation between chronic drug exposure and ΔFosB provides novel opportunities for targeted therapies in addiction (118), and suggests methods to analyze their efficacy (119). Over the past two decades, research has progressed from identifying ΔFosB induction to investigating its subsequent action (38). It is likely that ΔFosB research will now progress into a new era – the use of ΔFosB as a biomarker. …
    Conclusion
    ΔFosB is an essential transcription factor implicated in the molecular and behavioral pathways of addiction following repeated drug exposure. The formation of ΔFosB in multiple brain regions, and the molecular pathway leading to the formation of AP-1 complexes is well understood. The establishment of a functional purpose for ΔFosB has allowed further determination as to some of the key aspects of its molecular cascades, involving effectors such as GluR2 (87,88), Cdk5 (93) and NFkB (100). Moreover, many of these molecular changes identified are now directly linked to the structural, physiological and behavioral changes observed following chronic drug exposure (60,95,97,102). New frontiers of research investigating the molecular roles of ΔFosB have been opened by epigenetic studies, and recent advances have illustrated the role of ΔFosB acting on DNA and histones, truly as a molecular switch (34). As a consequence of our improved understanding of ΔFosB in addiction, it is possible to evaluate the addictive potential of current medications (119), as well as use it as a biomarker for assessing the efficacy of therapeutic interventions (121,122,124). Some of these proposed interventions have limitations (125) or are in their infancy (75). However, it is hoped that some of these preliminary findings may lead to innovative treatments, which are much needed in addiction.
  16. ^ une b c e F g h je j k l m m o p q r s t vous v w X oui z aa ab ac ad ae af ag ah ai aj ak al Olsen CM (December 2011). "Natural rewards, neuroplasticity, and non-drug addictions". Neuropharmacology. 61 (7): 1109–22. doi:10.1016/j.neuropharm.2011.03.010. PMC 3139704. PMID 21459101. Functional neuroimaging studies in humans have shown that gambling (Breiter et al, 2001), shopping (Knutson et al, 2007), orgasm (Komisaruk et al, 2004), playing video games (Koepp et al, 1998; Hoeft et al, 2008) and the sight of appetizing food (Wang et al, 2004a) activate many of the same brain regions (i.e., the mesocorticolimbic system and extended amygdala) as drugs of abuse (Volkow et al, 2004). … Cross-sensitization is also bidirectional, as a history of amphetamine administration facilitates sexual behavior and enhances the associated increase in NAc DA … As described for food reward, sexual experience can also lead to activation of plasticity-related signaling cascades. The transcription factor delta FosB is increased in the NAc, PFC, dorsal striatum, and VTA following repeated sexual behavior (Wallace et al., 2008; Pitchers et al., 2010b). This natural increase in delta FosB or viral overexpression of delta FosB within the NAc modulates sexual performance, and NAc blockade of delta FosB attenuates this behavior (Hedges et al, 2009; Pitchers et al., 2010b). Further, viral overexpression of delta FosB enhances the conditioned place preference for an environment paired with sexual experience (Hedges et al., 2009). … In some people, there is a transition from "normal" to compulsive engagement in natural rewards (such as food or sex), a condition that some have termed behavioral or non-drug addictions (Holden, 2001; Grant et al., 2006a). … In humans, the role of dopamine signaling in incentive-sensitization processes has recently been highlighted by the observation of a dopamine dysregulation syndrome in some patients taking dopaminergic drugs. This syndrome is characterized by a medication-induced increase in (or compulsive) engagement in non-drug rewards such as gambling, shopping, or sex (Evans et al, 2006; Aiken, 2007; Lader, 2008)."
    Table 1: Summary of plasticity observed following exposure to drug or natural reinforcers"
  17. ^ une b c e F Biliński P, Wojtyła A, Kapka-Skrzypczak L, Chwedorowicz R, Cyranka M, Studziński T (2012). "Epigenetic regulation in drug addiction". Anne. Agric. Environ. Med. 19 (3): 491–96. PMID 23020045. For these reasons, ΔFosB is considered a primary and causative transcription factor in creating new neural connections in the reward centre, prefrontal cortex, and other regions of the limbic system. This is reflected in the increased, stable and long-lasting level of sensitivity to cocaine and other drugs, and tendency to relapse even after long periods of abstinence. These newly constructed networks function very efficiently via new pathways as soon as drugs of abuse are further taken … In this way, the induction of CDK5 gene expression occurs together with suppression of the G9A gene coding for dimethyltransferase acting on the histone H3. A feedback mechanism can be observed in the regulation of these 2 crucial factors that determine the adaptive epigenetic response to cocaine. This depends on ΔFosB inhibiting G9a gene expression, i.e. H3K9me2 synthesis which in turn inhibits transcription factors for ΔFosB. For this reason, the observed hyper-expression of G9a, which ensures high levels of the dimethylated form of histone H3, eliminates the neuronal structural and plasticity effects caused by cocaine by means of this feedback which blocks ΔFosB transcription
  18. ^ une b c e F g h je j k l m Robison AJ, Nestler EJ (November 2011). "Transcriptional and epigenetic mechanisms of addiction". Nat. Rev. Neurosci. 12 (11): 623–37. doi:10.1038/nrn3111. PMC 3272277. PMID 21989194. ΔFosB has been linked directly to several addiction-related behaviors … Importantly, genetic or viral overexpression of ΔJunD, a dominant negative mutant of JunD which antagonizes ΔFosB- and other AP-1-mediated transcriptional activity, in the NAc or OFC blocks these key effects of drug exposure14,22–24. This indicates that ΔFosB is both necessary and sufficient for many of the changes wrought in the brain by chronic drug exposure. ΔFosB is also induced in D1-type NAc MSNs by chronic consumption of several natural rewards, including sucrose, high fat food, sex, wheel running, where it promotes that consumption14,26–30. This implicates ΔFosB in the regulation of natural rewards under normal conditions and perhaps during pathological addictive-like states.
  19. ^ une b Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 1: Basic Principles of Neuropharmacology". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. p. 4. ISBN 978-0-07-148127-4. Drug abuse and addiction exact an astoundingly high financial and human toll on society through direct adverse effects, such as lung cancer and hepatic cirrhosis, and indirect adverse effects –for example, accidents and AIDS – on health and productivity.
  20. ^ une b c Merikangas KR, McClair VL (June 2012). "Epidemiology of Substance Use Disorders". Hum. Genet. 131 (6): 779–89. doi:10.1007/s00439-012-1168-0. PMC 4408274. PMID 22543841.
  21. ^ une b c e F g "American Board of Medical Specialties recognizes the new subspecialty of addiction medicine" (PDF). American Board of Addiction Medicine. 14 March 2016. Récupéré 3 April 2016. Sixteen percent of the non-institutionalized U.S. population age 12 and over – more than 40 million Americans – meets medical criteria for addiction involving nicotine, alcohol or other drugs. This is more than the number of Americans with cancer, diabetes or heart conditions. In 2014, 22.5 million people in the United States needed treatment for addiction involving alcohol or drugs other than nicotine, but only 11.6 percent received any form of inpatient, residential, or outpatient treatment. Of those who do receive treatment, few receive evidence-based care. (There is no information available on how many individuals receive treatment for addiction involving nicotine.)
    Risky substance use and untreated addiction account for one-third of inpatient hospital costs and 20 percent of all deaths in the United States each year, and cause or contribute to more than 100 other conditions requiring medical care, as well as vehicular crashes, other fatal and non-fatal injuries, overdose deaths, suicides, homicides, domestic discord, the highest incarceration rate in the world and many other costly social consequences. The economic cost to society is greater than the cost of diabetes and all cancers combined. Despite these startling statistics on the prevalence and costs of addiction, few physicians have been trained to prevent or treat it.
  22. ^ "Economic consequences of drug abuse" (PDF). International Narcotics Control Board Report: 2013 (PDF). United Nations – International Narcotics Control Board. 2013. ISBN 978-92-1-148274-4. Récupéré 28 September 2018.
  23. ^ Morse RM, Flavin DK (August 1992). "The definition of alcoholism. The Joint Committee of the National Council on Alcoholism and Drug Dependence and the American Society of Addiction Medicine to Study the Definition and Criteria for the Diagnosis of Alcoholism". JAMA. 268 (8): 1012–14. doi:10.1001/jama.1992.03490080086030. PMID 1501306.
  24. ^ Marlatt GA, Baer JS, Donovan DM, Kivlahan DR (1988). "Addictive behaviors: etiology and treatment". Annu Rev Psychol. 39: 223–52. doi:10.1146/annurev.ps.39.020188.001255. PMID 3278676.
  25. ^ Gansner ME (12 September 2019). "Gaming Addiction in ICD-11: Issues and Implications". Psychiatric Times. Récupéré 3 March 2020.
  26. ^ une b American Psychiatric Association (2013). "Substance-Related and Addictive Disorders" (PDF). American Psychiatric Publishing. pp. 1–2. Archived from the original (PDF) on 15 August 2015. Récupéré 10 July 2015. Additionally, the diagnosis of dependence caused much confusion. Most people link dependence with "addiction" when in fact dependence can be a normal body response to a substance.
  27. ^ une b Malenka RC, Nestler EJ, Hyman SE, Holtzman DM (2015). "Chapter 16: Reinforcement and Addictive Disorders". Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (3rd ed.). New York: McGraw-Hill Medical. ISBN 978-0-07-182770-6. The official diagnosis of drug addiction by the Diagnostic and Statistic Manual of Mental Disorders (2013), which uses the term substance use disorder, is flawed. Criteria used to make the diagnosis of substance use disorders include tolerance and somatic dependence/withdrawal, even though these processes are not integral to addiction as noted. It is ironic and unfortunate that the manual still avoids use of the term addiction as an official diagnosis, even though addiction provides the best description of the clinical syndrome.
  28. ^ Washburn DA (2016). "The Stroop effect at 80: The competition between stimulus control and cognitive control". J Exp Anal Behav. 105 (1): 3–13. doi:10.1002/jeab.194. PMID 26781048. Today, arguably more than at any time in history, the constructs of attention, executive functioning, and cognitive control seem to be pervasive and preeminent in research and theory. Even within the cognitive framework, however, there has long been an understanding that behavior is multiply determined, and that many responses are relatively automatic, unattended, contention-scheduled, and habitual. Indeed, the cognitive flexibility, response inhibition, and self-regulation that appear to be hallmarks of cognitive control are noteworthy only in contrast to responses that are relatively rigid, associative, and involuntary.
  29. ^ Diamond A (2013). "Executive functions". Annu Rev Psychol. 64: 135–68. doi:10.1146/annurev-psych-113011-143750. PMC 4084861. PMID 23020641. Core EFs are inhibition (response inhibition (self-control – resisting temptations and resisting acting impulsively) and interference control (selective attention and cognitive inhibition)), working memory, and cognitive flexibility (including creatively thinking "outside the box," seeing anything from different perspectives, and quickly and flexibly adapting to changed circumstances). … EFs and prefrontal cortex are the first to suffer, and suffer disproportionately, if something is not right in your life. They suffer first, and most, if you are stressed (Arnsten 1998, Liston et al. 2009, Oaten & Cheng 2005), sad (Hirt et al. 2008, von Hecker & Meiser 2005), lonely (Baumeister et al. 2002, Cacioppo & Patrick 2008, Campbell et al. 2006, Tun et al. 2012), sleep deprived (Barnes et al. 2012, Huang et al. 2007), or not physically fit (Best 2010, Chaddock et al. 2011, Hillman et al. 2008). Any of these can cause you to appear to have a disorder of EFs, such as ADHD, when you do not. You can see the deleterious effects of stress, sadness, loneliness, and lack of physical health or fitness at the physiological and neuroanatomical level in prefrontal cortex and at the behavioral level in worse EFs (poorer reasoning and problem solving, forgetting things, and impaired ability to exercise discipline and self-control). …
    EFs can be improved (Diamond & Lee 2011, Klingberg 2010). … At any age across the life cycle EFs can be improved, including in the elderly and in infants. There has been much work with excellent results on improving EFs in the elderly by improving physical fitness (Erickson & Kramer 2009, Voss et al. 2011) … Inhibitory control (one of the core EFs) involves being able to control one's attention, behavior, thoughts, and/or emotions to override a strong internal predisposition or external lure, and instead do what's more appropriate or needed. Without inhibitory control we would be at the mercy of impulses, old habits of thought or action (conditioned responses), and/or stimuli in the environment that pull us this way or that. Thus, inhibitory control makes it possible for us to change and for us to choose how we react and how we behave rather than being unthinking creatures of habit. It doesn’t make it easy. Indeed, we usually are creatures of habit and our behavior is under the control of environmental stimuli far more than we usually realize, but having the ability to exercise inhibitory control creates the possibility of change and choice. … The subthalamic nucleus appears to play a critical role in preventing such impulsive or premature responding (Frank 2006).
  30. ^ une b Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 13: Higher Cognitive Function and Behavioral Control". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 313–21. ISBN 978-0-07-148127-4. • Executive function, the cognitive control of behavior, depends on the prefrontal cortex, which is highly developed in higher primates and especially humans.
    • Working memory is a short-term, capacity-limited cognitive buffer that stores information and permits its manipulation to guide decision-making and behavior. …
    These diverse inputs and back projections to both cortical and subcortical structures put the prefrontal cortex in a position to exert what is often called "top-down" control or cognitive control of behavior. … The prefrontal cortex receives inputs not only from other cortical regions, including association cortex, but also, via the thalamus, inputs from subcortical structures subserving emotion and motivation, such as the amygdala (Chapter 14) and ventral striatum (or nucleus accumbens; Chapter 15). …
    In conditions in which prepotent responses tend to dominate behavior, such as in drug addiction, where drug cues can elicit drug seeking (Chapter 15), or in attention deficit hyperactivity disorder (ADHD; described below), significant negative consequences can result. … ADHD can be conceptualized as a disorder of executive function; specifically, ADHD is characterized by reduced ability to exert and maintain cognitive control of behavior. Compared with healthy individuals, those with ADHD have diminished ability to suppress inappropriate prepotent responses to stimuli (impaired response inhibition) and diminished ability to inhibit responses to irrelevant stimuli (impaired interference suppression). … Functional neuroimaging in humans demonstrates activation of the prefrontal cortex and caudate nucleus (part of the striatum) in tasks that demand inhibitory control of behavior. Subjects with ADHD exhibit less activation of the medial prefrontal cortex than healthy controls even when they succeed in such tasks and utilize different circuits. … Early results with structural MRI show thinning of the cerebral cortex in ADHD subjects compared with age-matched controls in prefrontal cortex and posterior parietal cortex, areas involved in working memory and attention.
  31. ^ une b c Karila L, Wéry A, Weinstein A, Cottencin O, Petit A, Reynaud M, Billieux J (2014). "Sexual addiction or hypersexual disorder: different terms for the same problem? A review of the literature". Curr. Pharm. Des. 20 (25): 4012–20. doi:10.2174/13816128113199990619. PMID 24001295. Sexual addiction, which is also known as hypersexual disorder, has largely been ignored by psychiatrists, even though the condition causes serious psychosocial problems for many people. A lack of empirical evidence on sexual addiction is the result of the disease's complete absence from versions of the Diagnostic and Statistical Manual of Mental Disorders. … Existing prevalence rates of sexual addiction-related disorders range from 3% to 6%. Sexual addiction/hypersexual disorder is used as an umbrella construct to encompass various types of problematic behaviors, including excessive masturbation, cybersex, pornography use, sexual behavior with consenting adults, telephone sex, strip club visitation, and other behaviors. The adverse consequences of sexual addiction are similar to the consequences of other addictive disorders. Addictive, somatic and psychiatric disorders coexist with sexual addiction. In recent years, research on sexual addiction has proliferated, and screening instruments have increasingly been developed to diagnose or quantify sexual addiction disorders. In our systematic review of the existing measures, 22 questionnaires were identified. As with other behavioral addictions, the appropriate treatment of sexual addiction should combine pharmacological and psychological approaches.
  32. ^ une b c e Pitchers KK, Vialou V, Nestler EJ, Laviolette SR, Lehman MN, Coolen LM (February 2013). "Natural and drug rewards act on common neural plasticity mechanisms with ΔFosB as a key mediator". The Journal of Neuroscience. 33 (8): 3434–42. doi:10.1523/JNEUROSCI.4881-12.2013. PMC 3865508. PMID 23426671. Drugs of abuse induce neuroplasticity in the natural reward pathway, specifically the nucleus accumbens (NAc), thereby causing development and expression of addictive behavior. … Together, these findings demonstrate that drugs of abuse and natural reward behaviors act on common molecular and cellular mechanisms of plasticity that control vulnerability to drug addiction, and that this increased vulnerability is mediated by ΔFosB and its downstream transcriptional targets. … Sexual behavior is highly rewarding (Tenk et al., 2009), and sexual experience causes sensitized drug-related behaviors, including cross-sensitization to amphetamine (Amph)-induced locomotor activity (Bradley and Meisel, 2001; Pitchers et al., 2010a) and enhanced Amph reward (Pitchers et al., 2010a). Moreover, sexual experience induces neural plasticity in the NAc similar to that induced by psychostimulant exposure, including increased dendritic spine density (Meisel and Mullins, 2006; Pitchers et al., 2010a), altered glutamate receptor trafficking, and decreased synaptic strength in prefrontal cortex-responding NAc shell neurons (Pitchers et al., 2012). Finally, periods of abstinence from sexual experience were found to be critical for enhanced Amph reward, NAc spinogenesis (Pitchers et al., 2010a), and glutamate receptor trafficking (Pitchers et al., 2012). These findings suggest that natural and drug reward experiences share common mechanisms of neural plasticity
  33. ^ une b c e Beloate LN, Weems PW, Casey GR, Webb IC, Coolen LM (February 2016). "Nucleus accumbens NMDA receptor activation regulates amphetamine cross-sensitization and deltaFosB expression following sexual experience in male rats". Neuropharmacology. 101: 154–64. doi:10.1016/j.neuropharm.2015.09.023. PMID 26391065. S2CID 25317397.
  34. ^ Nehlig A (2004). Coffee, tea, chocolate, and the brain. Boca Raton: CRC Press. pp. 203–218. ISBN 9780429211928.
  35. ^ Meule A, Gearhardt AN (September 2014). "Food addiction in the light of DSM-5". Nutriments. 6 (9): 3653–71. doi:10.3390/nu6093653. PMC 4179181. PMID 25230209.
  36. ^ une b c Grant JE, Potenza MN, Weinstein A, Gorelick DA (September 2010). "Introduction to behavioral addictions". Un m. J. Drug Alcohol Abuse. 36 (5): 233–241. doi:10.3109/00952990.2010.491884. PMC 3164585. PMID 20560821. Naltrexone, a mu-opioid receptor antagonist approved by the US Food and Drug Administration for the treatment of alcoholism and opioid dependence, has shown efficacy in controlled clinical trials for the treatment of pathological gambling and kleptomania (76–79), and promise in uncontrolled studies of compulsive buying (80), compulsive sexual behavior (81), internet addiction (82), and pathologic skin picking (83). … Topiramate, an anti-convulsant which blocks the AMPA subtype of glutamate receptor (among other actions), has shown promise in open-label studies of pathological gambling, compulsive buying, and compulsive skin picking (85), as well as efficacy in reducing alcohol (86), cigarette (87), and cocaine (88) use. N-acetyl cysteine, an amino acid that restores extracellular glutamate concentration in the nucleus accumbens, reduced gambling urges and behavior in one study of pathological gamblers (89), and reduces cocaine craving (90) and cocaine use (91) in cocaine addicts. These studies suggest that glutamatergic modulation of dopaminergic tone in the nucleus accumbens may be a mechanism common to behavioral addiction and substance use disorders (92).
  37. ^ une b c e F g h je j k l m m o p Vassoler FM, Sadri-Vakili G (2014). "Mechanisms of transgenerational inheritance of addictive-like behaviors". Neuroscience. 264: 198–206. doi:10.1016/j.neuroscience.2013.07.064. PMC 3872494. PMID 23920159. However, the components that are responsible for the heritability of characteristics that make an individual more susceptible to drug addiction in humans remain largely unknown given that patterns of inheritance cannot be explained by simple genetic mechanisms (Cloninger et al., 1981; Schuckit et al., 1972). The environment also plays a large role in the development of addiction as evidenced by great societal variability in drug use patterns between countries and across time (UNODC, 2012). Therefore, both genetics and the environment contribute to an individual's vulnerability to become addicted following an initial exposure to drugs of abuse. …
    The evidence presented here demonstrates that rapid environmental adaptation occurs following exposure to a number of stimuli. Epigenetic mechanisms represent the key components by which the environment can influence genetics, and they provide the missing link between genetic heritability and environmental influences on the behavioral and physiological phenotypes of the offspring.
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    Figure 2: Psychostimulant-induced signaling events
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    Figure 4: Epigenetic basis of drug regulation of gene expression
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    G9a appears to be a critical control point for epigenetic regulation in NAc, as we know it functions in two negative feedback loops. It opposes the induction of ΔFosB, a long-lasting transcription factor important for drug addiction (Robison and Nestler, 2011), while ΔFosB in turn suppresses G9a expression (Maze et al., 2010; Sun et al., 2012a). … Also, G9a is induced in NAc upon prolonged HDAC inhibition, which explains the paradoxical attenuation of cocaine's behavioral effects seen under these conditions, as noted above (Kennedy et al., 2013). GABAA receptor subunit genes are among those that are controlled by this feedback loop. Thus, chronic cocaine, or prolonged HDAC inhibition, induces several GABAA receptor subunits in NAc, which is associated with increased frequency of inhibitory postsynaptic currents (IPSCs). In striking contrast, combined exposure to cocaine and HDAC inhibition, which triggers the induction of G9a and increased global levels of H3K9me2, leads to blockade of GABAA receptor and IPSC regulation.
  78. ^ une b c Blum K, Werner T, Carnes S, Carnes P, Bowirrat A, Giordano J, Oscar-Berman M, Gold M (2012). "Sex, drugs, and rock 'n' roll: hypothesizing common mesolimbic activation as a function of reward gene polymorphisms". Journal of Psychoactive Drugs. 44 (1): 38–55. doi:10.1080/02791072.2012.662112. PMC 4040958. PMID 22641964. It has been found that deltaFosB gene in the NAc is critical for reinforcing effects of sexual reward. Pitchers and colleagues (2010) reported that sexual experience was shown to cause DeltaFosB accumulation in several limbic brain regions including the NAc, medial pre-frontal cortex, VTA, caudate, and putamen, but not the medial preoptic nucleus. Next, the induction of c-Fos, a downstream (repressed) target of DeltaFosB, was measured in sexually experienced and naive animals. The number of mating-induced c-Fos-IR cells was significantly decreased in sexually experienced animals compared to sexually naive controls. Finally, DeltaFosB levels and its activity in the NAc were manipulated using viral-mediated gene transfer to study its potential role in mediating sexual experience and experience-induced facilitation of sexual performance. Animals with DeltaFosB overexpression displayed enhanced facilitation of sexual performance with sexual experience relative to controls. In contrast, the expression of DeltaJunD, a dominant-negative binding partner of DeltaFosB, attenuated sexual experience-induced facilitation of sexual performance, and stunted long-term maintenance of facilitation compared to DeltaFosB overexpressing group. Together, these findings support a critical role for DeltaFosB expression in the NAc in the reinforcing effects of sexual behavior and sexual experience-induced facilitation of sexual performance. … both drug addiction and sexual addiction represent pathological forms of neuroplasticity along with the emergence of aberrant behaviors involving a cascade of neurochemical changes mainly in the brain's rewarding circuitry.
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  94. ^ une b c Nestler EJ (October 2008). "Review. Transcriptional mechanisms of addiction: role of DeltaFosB". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 363 (1507): 3245–55. doi:10.1098/rstb.2008.0067. PMC 2607320. PMID 18640924. Recent evidence has shown that ΔFosB also represses the c-fos gene that helps create the molecular switch – from the induction of several short-lived Fos family proteins after acute drug exposure to the predominant accumulation of ΔFosB after chronic drug exposure – cited earlier (Renthal et al. in press). The mechanism responsible for ΔFosB repression of c-fos expression is complex and is covered below. …
    Examples of validated targets for ΔFosB in nucleus accumbens … GluR2 … dynorphin … Cdk5 … NFκB … c-Fos

    Table 3
  95. ^ une b c e F Berridge KC (April 2012). "From prediction error to incentive salience: mesolimbic computation of reward motivation". Eur. J. Neurosci. 35 (7): 1124–43. doi:10.1111/j.1460-9568.2012.07990.x. PMC 3325516. PMID 22487042. Here I discuss how mesocorticolimbic mechanisms generate the motivation component of incentive salience. Incentive salience takes Pavlovian learning and memory as one input and as an equally important input takes neurobiological state factors (e.g. drug states, appetite states, satiety states) that can vary independently of learning. Neurobiological state changes can produce unlearned fluctuations or even reversals in the ability of a previously learned reward cue to trigger motivation. Such fluctuations in cue-triggered motivation can dramatically depart from all previously learned values about the associated reward outcome. … Associative learning and prediction are important contributors to motivation for rewards. Learning gives incentive value to arbitrary cues such as a Pavlovian conditioned stimulus (CS) that is associated with a reward (unconditioned stimulus or UCS). Learned cues for reward are often potent triggers of desires. For example, learned cues can trigger normal appetites in everyone, and can sometimes trigger compulsive urges and relapse in addicts.
    Cue-triggered ‘wanting’ for the UCS
    A brief CS encounter (or brief UCS encounter) often primes a pulse of elevated motivation to obtain and consume more reward UCS. This is a signature feature of incentive salience.
    Cue as attractive motivational magnets
    When a Pavlovian CS+ is attributed with incentive salience it not only triggers ‘wanting’ for its UCS, but often the cue itself becomes highly attractive – even to an irrational degree. This cue attraction is another signature feature of incentive salience … Two recognizable features of incentive salience are often visible that can be used in neuroscience experiments: (i) UCS-directed ‘wanting’ – CS-triggered pulses of intensified ‘wanting’ for the UCS reward; and (ii) CS-directed ‘wanting’ – motivated attraction to the Pavlovian cue, which makes the arbitrary CS stimulus into a motivational magnet.
  96. ^ une b Malenka RC, Nestler EJ, Hyman SE (2009). Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 147–48, 366–67, 375–76. ISBN 978-0-07-148127-4. VTA DA neurons play a critical role in motivation, reward-related behavior (Chapter 15), attention, and multiple forms of memory. This organization of the DA system, wide projection from a limited number of cell bodies, permits coordinated responses to potent new rewards. Thus, acting in diverse terminal fields, dopamine confers motivational salience ("wanting") on the reward itself or associated cues (nucleus accumbens shell region), updates the value placed on different goals in light of this new experience (orbital prefrontal cortex), helps consolidate multiple forms of memory (amygdala and hippocampus), and encodes new motor programs that will facilitate obtaining this reward in the future (nucleus accumbens core region and dorsal striatum). In this example, dopamine modulates the processing of sensorimotor information in diverse neural circuits to maximize the ability of the organism to obtain future rewards. …
    The brain reward circuitry that is targeted by addictive drugs normally mediates the pleasure and strengthening of behaviors associated with natural reinforcers, such as food, water, and sexual contact. Dopamine neurons in the VTA are activated by food and water, and dopamine release in the NAc is stimulated by the presence of natural reinforcers, such as food, water, or a sexual partner. …
    The NAc and VTA are central components of the circuitry underlying reward and memory of reward. As previously mentioned, the activity of dopaminergic neurons in the VTA appears to be linked to reward prediction. The NAc is involved in learning associated with reinforcement and the modulation of motoric responses to stimuli that satisfy internal homeostatic needs. The shell of the NAc appears to be particularly important to initial drug actions within reward circuitry; addictive drugs appear to have a greater effect on dopamine release in the shell than in the core of the NAc. … If motivational drive is described in terms of wanting, and hedonic evaluation in terms of liking, it appears that wanting can be dissociated from liking and that dopamine may influence these phenomena differently. Differences between wanting and liking are confirmed in reports by human addicts, who state that their desire for drugs (wanting) increases with continued use even when pleasure (liking) decreases because of tolerance.
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  105. ^ Walter M, Dürsteler KM, Petitjean SA, Wiesbeck GA, Euler S, Sollberger D, Lang UE, Vogel M (2015). "(Psychosocial Treatment of Addictive Disorders – An Overview of Psychotherapeutic Options and their Efficacy)". Fortschr Neurol Psychiatr (en allemand). 83 (4): 201–10. doi:10.1055/s-0034-1399338. PMID 25893493. Addictive disorders are chronic relapsing conditions marked by compulsive and often uncontrolled use of psychotropic substances or stimuli. In this review, we present and discuss the current specific psychosocial interventions for addictive disorders and their effectiveness. In particular cognitive behavioral therapy, motivational interviewing, relapse prevention, the community reinforcement approach, and contingency management were found to be effective. For these psychotherapeutic treatments, mostly moderate effect sizes have been found. Their effectiveness seems to be highest in cannabis dependence. Empirical evidence for dependence on "hard" drugs is largest for contingency management, while for alcohol dependence motivational interviewing and the community reinforcement approach show the largest effect sizes. Presumably, combinations of different approaches as well as online interventions will bring further progress in the psychosocial treatment of addictive disorders in the future.
  106. ^ Carroll ME, Smethells JR (February 2016). "Sex Differences in Behavioral Dyscontrol: Role in Drug Addiction and Novel Treatments". Front. Psychiatry. 6: 175. doi:10.3389/fpsyt.2015.00175. PMC 4745113. PMID 26903885. Environmental Enrichment …
    In humans, non-drug rewards delivered in a contingency management (CM) format successfully reduced drug dependence … In general, CM programs promote drug abstinence through a combination of positive reinforcement for drug-free urine samples. For instance, voucher-based reinforcement therapy in which medication compliance, therapy session attendance, and negative drug screenings reinforced with vouchers to local business (e.g., movie theater, restaurants, etc.) directly reinforces drug abstinence, provides competing reinforcers, enriches the environment, and it is a robust treatment across a broad range of abused drugs (189). …
    Physical Exercise
    There is accelerating evidence that physical exercise is a useful treatment for preventing and reducing drug addiction … In some individuals, exercise has its own rewarding effects, and a behavioral economic interaction may occur, such that physical and social rewards of exercise can substitute for the rewarding effects of drug abuse. … The value of this form of treatment for drug addiction in laboratory animals and humans is that exercise, if it can substitute for the rewarding effects of drugs, could be self-maintained over an extended period of time. Work to date in (laboratory animals and humans) regarding exercise as a treatment for drug addiction supports this hypothesis. … However, a RTC study was recently reported by Rawson et al. (226), whereby they used 8 weeks of exercise as a post-residential treatment for METH addiction, showed a significant reduction in use (confirmed by urine screens) in participants who had been using meth 18 days or less a month. … Animal and human research on physical exercise as a treatment for stimulant addiction indicates that this is one of the most promising treatments on the horizon. (emphasis added)
  107. ^ une b c Lynch WJ, Peterson AB, Sanchez V, Abel J, Smith MA (September 2013). "Exercise as a novel treatment for drug addiction: a neurobiological and stage-dependent hypothesis". Neurosci Biobehav Rev. 37 (8): 1622–44. doi:10.1016/j.neubiorev.2013.06.011. PMC 3788047. PMID 23806439. (exercise) efficacy may be related to its ability to normalize glutamatergic and dopaminergic signaling and reverse drug-induced changes in chromatin via epigenetic interactions with brain-derived neurotrophic factor (BDNF) in the reward pathway. … these data show that exercise can affect dopaminergic signaling at many different levels, which may underlie its ability to modify vulnerability during drug use initiation. Exercise also produces neuroadaptations that may influence an individual's vulnerability to initiate drug use. Consistent with this idea, chronic moderate levels of forced treadmill running blocks not only subsequent methamphetamine-induced conditioned place preference, but also stimulant-induced increases in dopamine release in the NAc (Chen et al., 2008) and striatum (Marques et al., 2008). … (These) findings indicate the efficacy of exercise at reducing drug intake in drug-dependent individuals … wheel running (reduces) methamphetamine self-administration under extended access conditions (Engelmann et al., 2013) … These findings suggest that exercise may "magnitude"-dependently prevent the development of an addicted phenotype possibly by blocking/reversing behavioral and neuro-adaptive changes that develop during and following extended access to the drug. … Exercise has been proposed as a treatment for drug addiction that may reduce drug craving and risk of relapse. Although few clinical studies have investigated the efficacy of exercise for preventing relapse, the few studies that have been conducted generally report a reduction in drug craving and better treatment outcomes (see Table 4). … Taken together, these data suggest that the potential benefits of exercise during relapse, particularly for relapse to psychostimulants, may be mediated via chromatin remodeling and possibly lead to greater treatment outcomes.
  108. ^ une b Linke SE, Ussher M (2015). "Exercise-based treatments for substance use disorders: evidence, theory, and practicality". Am J Drug Alcohol Abuse. 41 (1): 7–15. doi:10.3109/00952990.2014.976708. PMC 4831948. PMID 25397661. The limited research conducted suggests that exercise may be an effective adjunctive treatment for SUDs. In contrast to the scarce intervention trials to date, a relative abundance of literature on the theoretical and practical reasons supporting the investigation of this topic has been published. … numerous theoretical and practical reasons support exercise-based treatments for SUDs, including psychological, behavioral, neurobiological, nearly universal safety profile, and overall positive health effects.
  109. ^ une b Zhou Y, Zhao M, Zhou C, Li R (July 2015). "Sex differences in drug addiction and response to exercise intervention: From human to animal studies". Front. Neuroendocrinol. 40: 24–41. doi:10.1016/j.yfrne.2015.07.001. PMC 4712120. PMID 26182835. Collectively, these findings demonstrate that exercise may serve as a substitute or competition for drug abuse by changing ΔFosB or cFos immunoreactivity in the reward system to protect against later or previous drug use. … As briefly reviewed above, a large number of human and rodent studies clearly show that there are sex differences in drug addiction and exercise. The sex differences are also found in the effectiveness of exercise on drug addiction prevention and treatment, as well as underlying neurobiological mechanisms. The postulate that exercise serves as an ideal intervention for drug addiction has been widely recognized and used in human and animal rehabilitation. … In particular, more studies on the neurobiological mechanism of exercise and its roles in preventing and treating drug addiction are needed.
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  171. ^ (1)(blank page?)
  172. ^ Culture Shock:Shopaholism (by Prachi Thanawala)
  173. ^ WWE: Inside WWE > News > Archive > Chris Jericho to rock Celebrity Duets:By: Jen Hunt Written: August 23, 2006

Further reading(Éditer)

Liens externes(Éditer)

Kyoto Encyclopedia of Genes and Genomes (KEGG) signal transduction pathways:


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