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Related Experiment Videos

Specific ethanol withdrawal seizures in genetically selected mice.

J D McSwigan, J C Crabbe, E R Young

    Life Sciences
    |November 19, 1984
    PubMed
    Summary

    Selective breeding created mice lines with differing susceptibility to ethanol withdrawal seizures. These lines exhibit specific differences in ethanol withdrawal seizure severity, not general central nervous system excitability, with one line showing enhanced ethanol anticonvulsant effects.

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    Genes, brain, and behavior·2013

    Area of Science:

    • Neuroscience
    • Genetics
    • Pharmacology

    Background:

    • Ethanol withdrawal can induce seizures, a significant clinical concern.
    • Genetic factors influence susceptibility to ethanol withdrawal seizures.
    • Understanding these genetic factors can inform therapeutic strategies.

    Purpose of the Study:

    • To investigate if selectively bred mice lines (WSP and WSR) differ in general central nervous system (CNS) excitability beyond ethanol withdrawal.
    • To determine if ethanol exhibits differential anticonvulsant effects in WSP and WSR mice.
    • To clarify the specificity of genetic selection for ethanol withdrawal seizure proneness.

    Main Methods:

    • Selective breeding of mice for ethanol withdrawal seizure proneness (WSP) and resistance (WSR).

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  • Assessment of generalized seizure thresholds using electroconvulsive shock (ECS), strychnine, and flurothyl.
  • Evaluation of ethanol's anticonvulsant effects against various seizure-inducing agents in WSP and WSR mice.
  • Determination of 50% effective dose (ED50) and 50% convulsant amperage (CA50) values.

    • Main Results:

    • No significant differences in seizure thresholds (CA50 for ECS, ED50 for drugs) were observed between WSP and WSR mice without ethanol pretreatment.
    • Ethanol pretreatment significantly enhanced the anticonvulsant effect against ECS in WSR mice compared to WSP mice.
    • Ethanol showed a greater anticonvulsant effect against strychnine and flurothyl in WSR mice, though the difference was less pronounced than for ECS.
    • Ethanol's effect on GABA antagonist-induced seizures did not differ between the lines.

    Conclusions:

    • Genetic selection successfully generated mouse lines with specific differences in ethanol withdrawal seizure severity.
    • The observed differences are specific to ethanol withdrawal and not due to generalized CNS hyperexcitability.
    • The WSR line exhibits a correlated response of increased sensitivity to ethanol's anticonvulsant properties.