Project: Research project

Project Details


This is a research program project whose objective is to understand the
biology of alcohol-seeking behavior (alcoholism). The research strategy is
to conduct interdisciplinary (biochemical-genetic, neurochemical,
neuroanatomical, neuroendocrine, and behavioral) studies in
selectively-bred rat lines that exhibit high (P and HAD lines) and low (NP
and LAD lines) voluntary ethanol consumption. The hypotheses to be tested
are that high alcohol-seeking behavior is associated with: 1) lower
threshold for the low-dose rewarding effects of ethanol, 2) higher
threshold for the aversive effects of ethanol, and 3) more rapid
development and longer persistence of tolerance to the highdose, aversive
effects of ethanol. The proximate goals of the program project are to
identify the neuronal, neurotransmitter, and neuroendocrine systems that
underlie these responses to ethanol. The ultimate goal is to identify the
genes responsible for the neurobiological abnormalities that lead to
abnormal alcohol-seeking behavior. There are 5 research components. (A) The
Animal and Molecular Genetics Component will continue the selective
breeding of the P, NP, HAD and LAD lines, search for new potential
biochemical (protein as well as DNA) markers of alcohol-preference, and
determine whether the known and yet-to-be-discovered associations of high
ethanol drinking preference are genetic by studies in animals from crosses
of the lines. (B) The Behavior and Behavioral Pharmacology Component will
explore-behavioral differences between P and NP rats other than those
related to alcohol and in response to other drugs. (C) The Neurochemistry
Component and (D) the Neuroanatomy Component will examine how P and NP rats
differ in serotonin (5HT), dopamine (DA), gamma-aminobutyric acid (GABA),
and glutamate (GLU) pathways and metabolism and how the metabolism of these
neurotransmitters are affected by ethanol in the P and NP rats. Methods to
be employed in these studies include quantitative autoradiography (receptor
ligand binding and (14)C-deoxyglucose uptake), microdialysis and HPLC
analysis of neurotransmitters and metabolites, in situ hybridization and
quantitative immunocytochemistry. Regions of particular interest are those
thought to be part of the brain reward circuitry. The Neuroendocrinology
Component (E) will examine the role of endogenous vasopressin (AVP) in
tolerance development and maintenance by comparing the synthesis (mRNA),
content and receptor binding of AVP in P and NP rats and how alcohol
affects these parameters in these lines. It will also examine how the
endogenous angiotensin (AII) system influences ethanol drinking.
Effective start/end date7/1/906/30/95


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)

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