Dopamine Release Patterns in Alcohol-drinking Behavior: An Optogenetic Study

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DESCRIPTION (provided by applicant): Alcohol is a widely abused, reinforcing drug. The success of developing effective treatments for alcohol abuse depends on a detailed understanding of the neurobiological changes involved in the development of addictive processes. Despite the evidence for the involvement of dopamine neurotransmission in the acute reinforcing and stimulating effects of alcohol, the role of dopamine release n alcohol drinking behavior is poorly understood. The goal of this study is to conduct the first examination of the role of physiological dopamine release patterns from defined striatal subregions on alcohol drinking behaviors in rats. We will selectively manipulate the pattern and location of dopamine release in the striatum of drinking rats using optogenetics. This cutting-edge technique will allow us to selectively stimulate dopaminergic neurons, in a precise temporal sequence, within very discrete subregions of the striatum (dorsal striatum, nucleus accumbens). Therefore, the causal relationships between specific dopamine release patterns, induced within these precise brain regions, and drinking behavior will be effectively explored. At the conclusion of this project, we will have identified DA release patterns (tonic versus phasic) and striatal subregions which increase or inhibit alcohol consumption. This functional mapping of the microcircuitry contributing to alcohol consumption will be critical for the developing effective treatment strategy for alcohol abuse. PUBLIC HEALTH RELEVANCE: The proposed work will bring together behavioral and electrochemical techniques along with genetic and optical approaches to address issues related to neurochemical mechanisms of alcohol addiction. The results of this study may potentially lead to new therapeutic strategies to dampen interest in alcohol drinking.