Too Difficult to Stop: Mechanisms Facilitating Relapse in Alcohol Dependence

Abstract

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.

Sex hormones in alcohol consumption: a systematic review of evidence

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A Functional Model of Fast Action Selection Guided by Emotional Stimuli

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“…One action ('I') thus conditioned to lead to the very positive outcome 'X' overcame other possible actions, a behavior similar to addiction [32]. On the opposite, an action leading to the trauma-like 'Z' was systematically avoided [33].…”

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“…Considerable efforts are made to alleviate the adverse effects of this epidemic, but most countries have not had noteworthy decreases in alcohol consumption per capita within the last 25 years 1 . Also, relapse rates among alcohol use disorder (AUD) patients have remained extremely high across different currently used therapeutic approaches, with often more than 50% 2 of patients consuming again after completing therapy (Garbusow et al, 2014; Naqvi and Morgenstern, 2015). Against this background, we are in dire need of better treatment options.…”