The Potent Effect of Environmental Context on Relapse to Alcohol- Seeking After Extinction

ABSTRACT

Environments in which the pharmacological effects of alcohol have been experienced become potent triggers for relapse in abstinent humans. Animal models developed to study the effect of environmental contexts on relapse to alcohol-seeking behavior demonstrate that alcohol-seeking is renewed by exposure to an alcohol-associated context, following the extinction of alcohol-seeking in a different context. Hence, contexts in which alcohol conditioning and extinction learning occur can be critical determinants for whether or not alcohol-seeking behavior is observed. This review summarizes preclinical research to date examining the role of alcohol contexts on the reinstatement of extinguished responding for alcohol. Behavioral studies have elucidated factors that are important for eliciting contextdependent relapse, and have uncovered novel interactions between alcohol-seeking driven by discrete alcohol cues in different contexts. Neuropharmacological studies provide substantial evidence for a role of dopaminergic systems in context-dependent reinstatement, and growing support for opioidergic mechanisms as well. Several key limbic brain regions have been identified in the modulation of alcohol-seeking by context, supporting a proposed neural circuit that includes the hippocampus, nucleus accumbens, basolateral amygdala, lateral hypothalamus, and the paraventricular thalamus.