Genetic correlations among inbred strain sensitivities to convulsions induced by 9 convulsant drugs

Ann E. Kosobud, John C. Crabbe

Research output: Contribution to journalArticle

126 Scopus citations

Abstract

Inbred mouse strains differed significantly in sensitivity to convulsions induced by 9 convulsant drugs administered using a timed infusion procedure. Some strains (e.g. BALB/cJ, A/J) were generally seizure-susceptible, while some were generally seizure resistant (e.g. C57BL/6J, SWR/J). However, the overall pattern of strain sensitivities was complex, and depended upon drug and convulsant sign. Five of the drugs (bicuculline, DMCM, picrotoxin, TBPS and pentylenetetrazol (PTZ)) produce convulsions, at least in part, through their interactions with the GABA receptor, while the other 4 (strychnine, CHEB, 4-aminopyridine and kainic acid) act through independent mechanisms. We predicted that responses to drugs with similar mechanisms of action would be genetically correlated. However, strains sensitive to picrotoxin-induced convulsions were not necessarily sensitive to convulsions elicited by PTZ or TBPS. Furthermore, different convulsant signs produced by a single drug were not always strongly correlated. Instead, genetic correlations were found among inbred strains for sensitivity to similar convulsant signs produced by different drugs. This suggests that genetic variation in sensitivity to these convulsant drugs arises primarily from variation in systems important for the expression of the convulsion.

Original languageEnglish (US)
Pages (from-to)8-16
Number of pages9
JournalBrain research
Volume526
Issue number1
DOIs
StatePublished - Aug 27 1990
Externally publishedYes

Keywords

  • Behavior genetics
  • Convulsant drug
  • Convulsion
  • Inbred Strain
  • Pharmacognetics
  • γ-Aminobutyric acid

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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