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Viral vector-induced amygdala NPY overexpression reverses increased alcohol intake caused by repeated deprivations in Wistar rats

Academic Article
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Overview

authors

  • Thorsell, A.
  • Repunte-Canonigo, Vez
  • O'Dell, L. E.
  • Chen, S. A.
  • King, A. R.
  • Lekic, D.
  • Koob, George
  • Sanna, Pietro

publication date

  • May 2007

journal

  • Brain  Journal

abstract

  • 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.

subject areas

  • Alcohol Drinking
  • Alcoholism
  • Amygdala
  • Animals
  • Anti-Anxiety Agents
  • Body Weight
  • Diet
  • Drinking
  • Gene Expression
  • Genetic Vectors
  • Male
  • Models, Animal
  • Neuropeptide Y
  • Rats
  • Rats, Wistar
  • Sindbis Virus
  • Transduction, Genetic
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Research

keywords

  • alcoholism
  • amygdala
  • animal model
  • neuropeptide Y
  • viral vector
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Identity

PubMed Central ID

  • PMC2749684

International Standard Serial Number (ISSN)

  • 0006-8950

Digital Object Identifier (DOI)

  • 10.1093/brain/awm033

PubMed ID

  • 17405766
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Additional Document Info

start page

  • 1330

end page

  • 1337

volume

  • 130

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