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

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.

• Authors: A E Kosobud, J C Crabbe
• Journal: Brain research (Brain Res) Vol. 526 Issue 1 Pg. 8-16 (Aug 27 1990) ISSN: 0006-8993 [Print] Netherlands
• PMID: 2078820 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Convulsants

Topics

• Animals
• Convulsants
• Genetic Predisposition to Disease
• Infusions, Intravenous
• Male
• Mice
• Mice, Inbred Strains
• Reaction Time (drug effects)
• Seizures (chemically induced, genetics)
• Species Specificity