Habit formation in a rodent model of alcoholism: Genetic susceptibility, alcohol-specific effects, and pharmacological manipulation

David S O'Tousa, Purdue University

Abstract

Habit formation is a well-characterized process involving a shift from response-outcome as the leading driving force underlying action to a stimulus-response mechanistic process. It is hypothesized that a transition from goal-directed behavior to habitual behavior is driven by a transition of the bulk of cognitive load from neocortical toward lower neurological mechanisms. While many neurotransmitter systems have a demonstrated involvement in this process, the dopamine system is particularly implicated. Habit formation is assessed through the maintenance of extinction responding for an undesired, or devalued, outcome. Theories relating the progression of addictive substance abuse, including alcohol use disorders, to the establishment of habitual action are characterized. Given the heritable nature of alcoholism, uncovering differences in habitual behavior among alcohol-preferring and non-preferring populations could inform future research into specific genetic mechanisms. Furthermore, according to recent evidence from rodent models, the involvement of alcohol in response-outcome motivated action facilitates the development of a habit, and the replication of these results in a heavier-drinking rodent model would elucidate the role of intoxication. Finally, research into putative pharmacotherapies in a model of habit susceptibility may prove beneficial. The current three experiments were designed to address these research goals. Two replicates each of high alcohol-preferring (HAP) and low-alcohol preferring (LAP) mice were tested using a palatable non-psychoactive reinforcer to assess genetic susceptibility. Crossed high-alcohol preferring mice (cHAP) mice were run using alcohol or sucrose as a reinforcer to assess alcohol-specific effects. Lastly, HAP mice were tested under systemic administration of flupenthixol, a dopaminergic antagonist, or control saline administration to assess the potential for pharmacological manipulation to influence habit formation. Results indicated that HAP2 mice formed habits rapidly, whereas LAP2 mice remained goal-directed; simultaneously, HAP3 mice required longer training to form habits whereas LAP3 mice remained goal-directed even after this extended training. cHAP mice did not demonstrate differences in habit formation involving alcohol compared to sucrose, but did achieve intoxication. Flupenthixol, in the highest dose tested, reduced overall levels of activity but did not alter habit formation in HAP2 mice. Importantly, these findings suggest that the susceptibility to form habits is genetically correlated with high alcohol preference. Also, these results do not support a role of high intoxication in facilitating habit formation, suggesting that the results observed elsewhere may be due to other properties of alcohol. Finally, these findings do not suggest that dopamine antagonism reduces habit formation in HAP mice, indicating that other neurotransmitter systems may be more salient in regulating habit formation in this population. Future research should seek to clarify neural and genetic mechanisms underlying these novel research outcomes.

Degree

Ph.D.

Advisors

Grahame, Purdue University.

Subject Area

Neurosciences|Psychobiology|Behavioral Sciences

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