Psychological and neural mechanisms of relapse

Abstract

Relapse, the resumption of drug taking after periods of abstinence, remains the major problem for the treatment of addiction. Even when drugs are unavailable for long periods or when users are successful in curbing their drug use for extended periods, individuals remain vulnerable to events that precipitate relapse. Behavioural studies in humans and laboratory animals show that drug-related stimuli, drugs themselves and stressors are powerful events for the precipitation of relapse. Molecular, neurochemical and anatomical studies have identified lasting neural changes that arise from mere exposure to drugs and other enduring changes that arise from learning about the relationship between drug-related stimuli and drug effects. Chronic drug exposure increases sensitivity of some systems of the brain to the effects of drugs and stressful events. These changes, combined with those underlying conditioning and learning, perpetuate vulnerability to drug-related stimuli. Circuits of the brain involved are those of the mesocorticolimbic dopaminergic system and its glutamatergic connections, and the corticotropin-releasing factor and noradrenergic systems of the limbic brain. This paper reviews advances in our understanding of how these systems mediate the effects of events that precipitate relapse and of how lasting changes in these systems can perpetuate vulnerability to relapse.

Stress and Alcohol Cues Exert Conjoint Effects on Go and Stop Signal Responding in Male Problem Drinkers

“…Relapse is a critical challenge in the management of addictive behavior (Stewart, 2008;Witkiewitz and Marlatt, 2007). Stress and exposure to drug-related cues are common relapse triggers (Shaham et al, 2003;Sinha and Li, 2007).…”

Neuroanatomical Structures Underlying the Extinction of Drug-Seeking Behavior

“…Drug-seeking behavior can be reinstated by several stimuli including a priming injection of the drug, presentation of drug-associated environmental stimuli, or exposure to an acute stressor without the need for additional behavioral training in a phenomenon known as reinstatement [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. The fact that no added behavioral training is necessary suggests that a memory trace of the original association remains intact.…”

Neurobiologie de la toxicomanie : avancées récentes et nouvelles stratégies d’intervention

“…Le système glutamatergique semble crucial quant aux processus neurobiologiques qui expliquent ces phénomènes. Les modèles animaux ont permis d'identifier ces processus, en imitant de façon relativement fidèle le développement d'une toxicomanie chez l'humain (Haney et Spealman, 2008 ;Stewart, 2008). Dans un de ces paradigme, l'animal contrôle la prise de substance (en appuyant sur un levier, ce qui entraîne l'administration d'une dose de drogue) et peut donc être étudié pendant les différentes phases de la dépendance : l'acquisition, la prise continue de drogue, le sevrage, l'abstinence et la rechute.…”

“…La recherche de substance suivant l'exposition à une drogue implique l'innervation dopaminergique du cortex préfrontal médian (CPFm) et de la coquille du NAc en provenance de l'aire tegmentale ventrale (ATV), mais également les projections glutamatergiques du CPFm au NAc et à l'ATV. Quant à la rechute liée à des stimuli associés à la prise de drogue, tant les projections dopaminergiques de l'ATV à l'amygdale basolatérale (ABL), au CPFm et au coeur du NAc que l'innervation glutamatergique du CPF et de l'ABL au NAc, et du CPF à l'ATV, sont impliquées (Feltenstein et See, 2008 ;Stewart, 2008). Peu importe la substance abusée, les études animales et humaines ont montré que le stress est aussi un des facteurs impliqués dans la rechute (Sinha et Li, 2007), parfois davantage que la prise de drogue elle-même (Shaham et coll., 1997).…”