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Selective breeding for alcohol withdrawal severity

J C Crabbe1, T J Phillips

  • 1Research Service, Department of Veterans Affairs Medical Center, Portland, Oregon 97201.

Behavior Genetics
|March 1, 1993
PubMed
Summary
This summary is machine-generated.

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Researchers developed alcohol withdrawal seizure prone (WSP) and resistant (WSR) mouse lines. Genetic studies reveal dominance for withdrawal resistance and suggest shared genes for alcohol and drug dependence severity.

Area of Science:

  • Neuroscience
  • Genetics
  • Pharmacology

Background:

  • Genetic selection created distinct mouse lines for alcohol withdrawal seizure proneness (WSP) and resistance (WSR).
  • The selection criterion was the severity of handling-induced convulsions following chronic ethanol exposure cessation.

Purpose of the Study:

  • To review behavioral, pharmacological, and neurochemical findings from a replicated bidirectional selection project.
  • To investigate genetic factors influencing alcohol withdrawal severity and cross-dependence susceptibility.

Main Methods:

  • Bidirectional genetic selection of mice based on withdrawal seizure severity.
  • Reciprocal F1 crosses between WSP and WSR lines.
  • Behavioral, pharmacological, and neurochemical analyses.

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Main Results:

  • Reciprocal crosses demonstrated substantial genetic dominance for resistance to alcohol withdrawal.
  • WSP and WSR lines exhibit significant differences in withdrawal severity from ethanol and other depressant drugs.
  • Genes influencing withdrawal severity appear to pleiotropically affect susceptibility to dependence on other drugs of abuse.

Conclusions:

  • Genetic factors controlling alcohol withdrawal severity in mice also influence cross-dependence to other drugs.
  • Separate genetic mechanisms likely control ethanol sensitivity and tolerance development compared to withdrawal severity.