Involvement and neuroplasticity of cholinergic interneurons of the nucleus accumbens in initiation and excessive alcohol drinking

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Title: Involvement and neuroplasticity of cholinergic interneurons of the nucleus accumbens in initiation and excessive alcohol drinking
Author: Camp, Marguerite Charlotte, 1980-
Abstract: Alcoholism is a complex disease that exists as a specific set of behaviors , such as the preoccupation with obtaining alcohol and compulsive alcohol drinking . Currently , more than 18 million adults in the United States suffer from alcohol abuse or alcoholism . This disease poses serious medical and economic consequences for society . Identifying the neurobiological mechanisms that underlie alcohol drinking , specifically the transition from initiation to binge drinking is critical for improved treatments for alcoholics and the vulnerability for relapse in those recovering . Many studies have identified brain regions and molecular mechanisms that underlie various stages of alcohol abuse ; however few have investigated the role of specific cell types within these areas . The overarching hypothesis of the studies in this dissertation is that cholinergic interneurons of the nucleus accumbens (NAc ) are key neural substrates that underlie alcohol drinking , and as drinking continues ; neuroadaptations within these cells then facilitate such behaviors as compulsive alcohol drinking . More specifically , these studies tested whether 1 ) cholinergic cell ablation in the NAc causes a decrease in alcohol drinking in C57BL /6J mice , 2 ) neuroadaptive changes in dopamine (DA ) D2 receptor and cyclin dependent kinase 5 (Cdk5 ) occur within these cells following initiation alcohol drinking , and to a greater extent following binge alcohol drinking in C57BL /6J mice , and 3 ) neuroadaptive changes in DA D2 receptor and Cdk5 also occur in brain regions that have been implicated in the rewarding and reinforcing effects of alcohol in inbred alcohol -preferring (iP ) rats . The present findings report a causal role for accumbal cholinergic neurons in binge alcohol drinking and identify DA D2 receptor and Cdk5 neuroadaptations following initiation and binge alcohol drinking . These studies identify the involvement of cholinergic interneurons in binge drinking and reveal alcohol -induced region - and cell -specific receptor and molecular changes that occur with continued drinking . These findings contribute to the understanding of the neurobiological mechanisms that underlie alcohol drinking , and provide the basis for cholinergic targeted treatments designed to attenuate binge drinking . These data also provide the groundwork for future studies aimed to examine receptor and intracellular molecular changes that occur with compulsive alcohol drinking , craving , and relapse .
URI: http : / /hdl .handle .net /2152 /3551
Date: 2008-08-28

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Involvement and neuroplasticity of cholinergic interneurons of the nucleus accumbens in initiation and excessive alcohol drinking. Doctoral dissertation, The University of Texas at Austin. Available electronically from http : / /hdl .handle .net /2152 /3551 .

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