Brain Advance Access first published online on April 2, 2007
This version published online on April 17, 2007
Brain, doi:10.1093/brain/awm033
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Viral vector-induced amygdala NPY overexpression reverses increased alcohol intake caused by repeated deprivations in Wistar rats
Molecular and Integrative Neurosciences Department, The Scripps Research Institute, La Jolla, CA, USA Present addresses: 1Laboratory of Clinical and Translational Studies, Section of Molecular Pathophysiology, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA, 2Department of Psychology, University of Texas, El Paso, TX, USA and 3Laboratory of Clinical and Translational Studies, National Institute on Alcohol Abuse and Alcoholism, Poolesville, MD, USA
Correspondence to:
George F. Koob, Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 North Torrey Pines Road SP30-2400, La Jolla, CA 92037, USA E-mail: gkoob{at}scripps.edu
Acute administration of neuropeptide Y (NPY) modulates alcohol intake in genetic and chemical models of high intake, while leaving intake unaffected during ‘normal’ or baseline conditions. In non-selected, normal rat lines, alcohol consumption can be increased by prolonged exposure to alcohol, and it is unclear what effect a constitutive increase in NPY function will have on alcohol intake. The purpose of the present study was to examine the effects on alcohol intake of an inducible, constitutive overexpression of NPY, one of the most abundant neuropeptides in the central nervous system. A liquid diet was used in combination with repeated alcohol deprivation sessions to increase alcohol intake in normal Wistar rats. We then examined the effect of NPY overexpression in the amygdala on excessive alcohol intake produced by prolonged exposure to alcohol and alcohol deprivation. Repeated withdrawal increased alcohol consumption in a 24-h continuous access two-bottle choice model. Both the number of withdrawals as well as the length of the withdrawal periods affected alcohol consumption with an increased intake resulting from multiple withdrawals and the alcohol deprivation effect being enhanced by longer periods of abstinence. The increase in intake following repeated abstinence was blunted by intra-amygdala administration of a Sindbis viral vector containing NPY cDNA. Amygdala NPY overexpression also was demonstrated to be anxiolytic in the open field test. Repeated withdrawal in combination with a history of alcohol consumption significantly elevated alcohol intake, and the amygdala may mediate the transition to high-drinking states in this model.
Key Words: alcoholism; animal model; neuropeptide Y; viral vector; amygdala
Abbreviations: ADE, alcohol deprivation effect; BHK, Baby Hamster Kidney; GFP, green fluorescent protein; HAD, high alcohol drinking; NPY, neuropeptide Y
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Received July 6, 2006. Revised February 2, 2007. Accepted February 12, 2007.
*These authors contributed equally to this work.
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