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Chronic alcohol alters rewarded behaviors and striatal plasticity.

ABSTRACT: Chronic intermittent ethanol (CIE) alters neural functions and behaviors mediated by the dorsolateral striatum (DLS) and prefrontal cortex. Here, we examined the effects of prolonged (16-bout) CIE on DLS plasticity and DLS-mediated behaviors. Ex vivo electrophysiological recordings revealed loss in efficacy of DLS synaptically induced activation and absent long-term depression after CIE. CIE increased two-bottle choice drinking and impaired Pavlovian-to-instrumental transfer but not discriminated approach. These data suggest prolonged CIE impaired DLS plasticity, to produce associated changes in drinking and cue-controlled reward-seeking. Given recent evidence that less-prolonged CIE can promote certain dorsal striatal-mediated behaviors, CIE may drive chronicity-dependent adaptations in corticostriatal systems regulating behavior.

SUBMITTER: DePoy L

PROVIDER: S-EPMC4177024 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Chronic alcohol alters rewarded behaviors and striatal plasticity.

DePoy Lauren L Daut Rachel R Wright Tara T Camp Marguerite M Crowley Nicole N Noronha Bianca B Lovinger David D Holmes Andrew A

Addiction biology 20140326 2

Chronic intermittent ethanol (CIE) alters neural functions and behaviors mediated by the dorsolateral striatum (DLS) and prefrontal cortex. Here, we examined the effects of prolonged (16-bout) CIE on DLS plasticity and DLS-mediated behaviors. Ex vivo electrophysiological recordings revealed loss in efficacy of DLS synaptically induced activation and absent long-term depression after CIE. CIE increased two-bottle choice drinking and impaired Pavlovian-to-instrumental transfer but not discriminate ...[more]

PMID: 24666522

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Project description:BackgroundAlcohol withdrawal is a key component of severe alcohol use disorder. Animal models of alcohol withdrawal tend to focus on traditional anxiety/stress tests. While these have been essential to advancing our understanding of the biology of alcohol withdrawal, abrupt cessation of drinking following heavy alcohol consumption can also trigger withdrawal-related affective states that impact responses to a variety of life events and stressors. To this end, we show that behaviors in a variety of tasks that differ in task demand and intensity are altered during withdrawal in male and female mice after voluntary alcohol access.MethodsMale and female miceunderwent six weeks of intermittent two-bottle choice alcohol exposure followed by behavioral tests. The tests included-Home cage: low-stress baseline environment to measure spontaneous natural behaviors; Open field: anxiety-inducing bright novel environment; Looming disc: arena with a protective hut where mice are exposed to a series of discs that mimic an overhead advancing predator, and Robogator-simulated predator task: forced foraging behavioral choice in the presence of an advancing robot predator that "attacks" when mice are near a food pellet in a large open arena.ResultsA history of alcohol exposure impacted behaviors in these tasks in a sex-dependent manner. In the home cage, alcohol induced reductions in digging and heightened stress coping through an increase in grooming time. In males, increased rearing yielded greater vigilance/exploration in a familiar environment. The open-field test revealed an anxiety phenotype in both male and female mice exposed to alcohol. Male mice showed no behavioral alterations to the looming disc task, while females exposed to alcohol showed greater escape responses than water controls, indicative of active stress-response behaviors. In males, the Robogator task revealed a hesitant/avoidant phenotype in alcohol-exposed mice under greater task demands.ConclusionsFew drugs show robust evidence of efficacy in clinical trials for alcohol withdrawal. Understanding how withdrawal alters a variety of behaviors in both males and females that are linked to stress coping can increase our understanding of alcohol misuse and aid in developing better medications for treating individuals with AUD.

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Chronic alcohol alters rewarded behaviors and striatal plasticity.

Publications

Chronic alcohol alters rewarded behaviors and striatal plasticity.

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