Individual differences in the engagement of habitual control over alcohol seeking predict the development of compulsive alcohol seeking and drinking

Abstract

Excessive drinking is an important behavioural characteristic of alcohol addiction, but not the only one. Individuals addicted to alcohol crave alcoholic beverages, spend time seeking alcohol despite negative consequences and eventually drink to intoxication. With prolonged use, control over alcohol seeking devolves to anterior dorsolateral striatum, dopamine‐dependent mechanisms implicated in habit learning and individuals in whom alcohol seeking relies more on these mechanisms are more likely to persist in seeking alcohol despite the risk of punishment. Here, we tested the hypothesis that the development of habitual alcohol seeking predicts the development of compulsive seeking and that, once developed, it is associated with compulsive alcohol drinking. Male alcohol‐preferring rats were pre‐exposed intermittently to a two‐bottle choice procedure and trained on a seeking–taking chained schedule of alcohol reinforcement until some individuals developed punishment‐resistant seeking behaviour. The associative basis of their seeking responses was probed with an outcome‐devaluation procedure, early or late in training. After seeking behaviour was well established, subjects that had developed greater resistance to outcome devaluation (were more habitual) were more likely to show punishment‐resistant (compulsive) alcohol seeking. These individuals also drank more alcohol, despite quinine adulteration, even though having similar alcohol preference and intake before and during instrumental training. They were also less sensitive to changes in the contingency between seeking responses and alcohol outcome, providing further evidence of recruitment of the habit system. We therefore provide direct behavioural evidence that compulsive alcohol seeking emerges alongside compulsive drinking in individuals who have preferentially engaged the habit system.

Striatal dopamine signals are region specific and temporally stable across action-sequence habit formation

“…Notably, the test consistently and reliably exposed the gradual nature of the change in lever preference across training weeks in several cohorts of animals ( Figure S2 A). The slow speed at which the preference shift develops is another validating feature (as reported in other seeking-taking studies 59 , 60 ), as habits in humans are thought to form slowly via extensive repetition. 3 , 42 , 61 , 62 Moreover, the test demonstrated that within the same animals, via overtraining, habit-like performance can arise out of a behavior that was initially under goal-directed control; 61 , 62 overtraining has been shown to effectively produce habits, both in single-action and action-sequence tasks, but aspects of action sequences (e.g., initiation or termination) may remain under goal-directed or mixed control (the latter may explain that no-habit rats do not exhibit a lever preference in week 10).…”

The development of compulsive coping behaviors depends on the engagement of dorsolateral striatum dopamine-dependent mechanisms

“…We then sought to identify the neural locus of control of such coping behavior that appears to be initially goal-directed, the goal of the response (drinking) being the alleviation of distress (14, 22, 76), but eventually becomes excessive and compulsive (74, 77, 78), a transition hypothesized here to reflect the development of maladaptive negative-reinforcement driven habits. Thus, we assessed the reliance of adjunctive fluid drinking on aDLS DA, a signature of habitual control over alcohol-related responding (79), and the compulsion to seek and drink alcohol (57, 58).…”

“…However, the psychological and neural basis of the individual vulnerability to lose control over coping behaviors, involving alcohol use or not, and the ensuing development of compulsivity have not been defined. Increasing evidence suggests that the transition from controlled goal-directed behaviors to compulsion, including the compulsive seeking and drinking of alcohol (57, 58) and the development of compulsive adjunctive polydipsic drinking, is dependent on a shift in the locus of control over behavior from the ventral to the dorsolateral striatum (DLS)-dependent habit system (59). Thus, while the reinforcing properties of alcohol mediated by the mesolimbic system support recreational alcohol use (60, 61), it is the engagement of anterior DLS (aDLS) dopamine (DA) dependent alcohol seeking habits that promotes the transition to compulsive alcohol seeking and drinking (57, 58, 61).…”

“…Increasing evidence suggests that the transition from controlled goal-directed behaviors to compulsion, including the compulsive seeking and drinking of alcohol (57, 58) and the development of compulsive adjunctive polydipsic drinking, is dependent on a shift in the locus of control over behavior from the ventral to the dorsolateral striatum (DLS)-dependent habit system (59). Thus, while the reinforcing properties of alcohol mediated by the mesolimbic system support recreational alcohol use (60, 61), it is the engagement of anterior DLS (aDLS) dopamine (DA) dependent alcohol seeking habits that promotes the transition to compulsive alcohol seeking and drinking (57, 58, 61). Similarly, the development of adjunctive polydipsic water drinking behavior, but not its compulsive manifestation, is dependent on the mesolimbic system (62, 63) while well-established excessive, compulsive adjunctive water drinking in vulnerable individuals has been associated with an increased in spine density in DLS medium spiny neurons (64).…”

A Systematic Review of Exercise Intervention Program for People With Substance Use Disorder

“…Individuals addicted to alcohol crave alcoholic beverages, spend time seeking alcohol despite negative consequences and eventually drink to intoxication. With prolonged use, control over alcohol seeking devolves to dopamine-dependent mechanisms implicated in habit learning and individuals in whom alcohol seeking relies more on these mechanisms are more likely to persist in seeking alcohol despite the risk of punishment ( 8 ). Clinical studies have shown that exercise can be used as a potential intervention tool for substance use disorder, producing beneficial and durable protection in all stages of substance use disorder.…”