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Proc Natl Acad Sci U S A. 2013 Sep 3;110(36):14783-8. doi: 10.1073/pnas.1308198110. Epub 2013 Aug 19.

Chronic alcohol produces neuroadaptations to prime dorsal striatal learning.

Author information

1
Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcoholism and Alcohol Abuse, National Institutes of Health, Bethesda, MD 20814, USA.

Abstract

Drug addictions including alcoholism are characterized by degradation of executive control over behavior and increased compulsive drug seeking. These profound behavioral changes are hypothesized to involve a shift in the regulation of behavior from prefrontal cortex to dorsal striatum (DLS). Studies in rodents have shown that ethanol disrupts cognitive processes mediated by the prefrontal cortex, but the potential effects of chronic ethanol on DLS-mediated cognition and learning are much less well understood. Here, we first examined the effects of chronic EtOH on DLS neuronal morphology, synaptic plasticity, and endocannabinoid-CB1R signaling. We next tested for ethanol-induced changes in striatal-related learning and DLS in vivo single-unit activity during learning. Mice exposed to chronic intermittent ethanol (CIE) vapor exhibited expansion of dendritic material in DLS neurons. Following CIE, DLS endocannabinoid CB1 receptor signaling was down-regulated, and CB1 receptor-dependent long-term depression at DLS synapses was absent. CIE mice showed facilitation of DLS-dependent pairwise visual discrimination and reversal learning, relative to air-exposed controls. CIE mice were also quicker to extinguish a stimulus-reward instrumental response and faster to reduce Pavlovian approach behavior under an omission schedule. In vivo single-unit recording during learning revealed that CIE mice had augmented DLS neuronal activity during correct responses. Collectively, these findings support a model in which chronic ethanol causes neuroadaptations in the DLS that prime for greater DLS control over learning. The shift to striatal dominance over behavior may be a critical step in the progression of alcoholism.

KEYWORDS:

PFC; abuse; cannabinoid; dependence; touchscreen

PMID:
23959891
PMCID:
PMC3767559
DOI:
10.1073/pnas.1308198110
[Indexed for MEDLINE]
Free PMC Article
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