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Related Experiment Videos

Genetic components of ethanol responses.

J C Crabbe1, D J Feller, E S Terdal

  • 1Research Service, VA Medical Center, Portland, OR 97201.

Alcohol (Fayetteville, N.Y.)
|May 1, 1990
PubMed
Summary

Selective breeding of animals reveals genetic influences on ethanol (EtOH) responses. Different mouse lines show varied sensitivities, implicating specific neurotransmitter systems in EtOH-induced hypothermia but not withdrawal seizures.

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Area of Science:

  • Neuroscience
  • Behavioral Pharmacology
  • Genetics

Background:

  • Understanding ethanol (EtOH) effects relies on identifying neurotransmitter roles.
  • Selective breeding of animal lines offers a powerful method to study genetic contributions to EtOH responses.
  • Differences between selected lines can reveal pleiotropic gene actions influencing complex behaviors.

Purpose of the Study:

  • To investigate the role of specific neurotransmitter systems in mediating ethanol's behavioral effects using selectively bred mouse lines.
  • To determine if genetic factors influencing EtOH-induced hypothermia are linked to particular neurotransmitter systems.
  • To assess the neurotransmitter basis for differences in handling-induced convulsions (HIC) following ethanol withdrawal.

Main Methods:

  • Behavioral pharmacological experiments were conducted on two sets of selectively bred mouse lines: Withdrawal Seizure-Prone (WSP) and -Resistant (WSR), and COLD and HOT mice.
  • WSP/WSR lines were selected for high/low handling-induced convulsions after chronic ethanol inhalation.
  • COLD/HOT lines were selected for severe/mild hypothermia after acute ethanol administration; sensitivity to various drugs targeting neurotransmitter systems was assessed.

Main Results:

  • WSP mice exhibited greater sensitivity to convulsant drugs compared to WSR mice, with no clear link to a single neurotransmitter system.
  • COLD mice showed increased sensitivity to opioid and serotonergic drugs, suggesting these systems are involved in ethanol-induced hypothermia.
  • COLD and HOT mice did not differ in sensitivity to dopaminergic, alpha-adrenergic, or nicotinic acetylcholinergic drugs.

Conclusions:

  • Genetic determination of ethanol withdrawal seizures is not attributable to a single neurotransmitter system.
  • Opioid and serotonergic systems are likely involved in ethanol-induced hypothermia, as indicated by differential drug sensitivities in COLD and HOT mice.
  • Selective breeding provides a valuable tool for dissecting the neurochemical underpinnings of ethanol's complex behavioral effects.

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