Learning processes in relapse to alcohol use: lessons from animal models

Abstract

Rationale: Alcohol use is reliably preceded by discrete and contextual stimuli which, through diverse learning processes, acquire the capacity to promote alcohol use and relapse to alcohol use.

Objective: We review contemporary extinction, renewal, reinstatement, occasion setting, and sex differences research within a conditioning framework of relapse to alcohol use to inform the development of behavioural and pharmacological therapies.

Key findings: Diverse learning processes and corresponding neurobiological substrates contribute to relapse to alcohol use. Results from animal models indicate that cortical, thalamic, accumbal, hypothalamic, mesolimbic, glutamatergic, opioidergic, and dopaminergic circuitries contribute to alcohol relapse through separable learning processes. Behavioural therapies could be improved by increasing the endurance and generalizability of extinction learning and should incorporate whether discrete cues and contexts influence behaviour through direct excitatory conditioning or occasion setting mechanisms. The types of learning processes that most effectively influence responding for alcohol differ in female and male rats.

Conclusion: Sophisticated conditioning experiments suggest that diverse learning processes are mediated by distinct neural circuits and contribute to relapse to alcohol use. These experiments also suggest that gender-specific behavioural and pharmacological interventions are a way towards efficacious therapies to prevent relapse to alcohol use.

Keywords: Conditioning; Context; Cue; Ethanol; Extinction; Occasion setting; Pavlovian conditioning; Reinstatement; Renewal; Sex differences.