Too Difficult to Stop: Mechanisms Facilitating Relapse in Alcohol Dependence

Background: In alcohol and other substance dependencies, patients often suffer relapse despite better knowledge and their intention to remain abstinent. A variety of neurotransmitter systems and their respective alterations due to the chronic drug intake are involved in mechanisms that facilitate relapse. It has been postulated that these neurotransmitter systems are related to changes in motivational and learning mechanisms, and engender a shift from goal-directed to habitual behavior in dependent patients that facilitates drug-seeking behavior. Methods: We review learning mechanisms facilitating relapse, as identified and tested to date. We focus on studies examining the interaction between alcohol-related changes in monoaminergic neurotransmission and their respective effects on pavlovian and operant learning mechanisms in alcohol dependence. Results: Animal experiments and first human studies suggest that chronic alcohol intake impairs goal-directed behavior and facilitates habitual drug intake. Key symptoms of alcohol dependence such as tolerance development, withdrawal, craving and reduced control of alcohol intake can be explained by alcohol-induced alteration of dopaminergic neurotransmission and its GABAergic and glutamatergic modulation and their respective effects on pavlovian and operant conditioning as well as pavlovian-to-instrumental transfer. Conclusion: Chronic alcohol intake impairs neurotransmitter systems that regulate prefrontal-striatal circuits and interfere with goal-directed decision-making and the acquisition of new, non-drug-related behavior patterns. Alcohol craving induced by pavlovian conditioned cues can facilitate habitual drug intake. Such learning mechanisms and their alterations by chronic alcohol intake might be targeted by specific interventions.