Genetic influences on GABA-related seizures

Genetic differences in susceptibility to chemically induced seizures were examined in various populations of mice. Three inbred strains: C57BL, DBA, and C3H and a heterogenous stock (HS) of mice were tested for sensitivity to seizures induced by 3-mercaptopropionic acid (MP) and flurothyl. Dose response curves were constructed for each population of mice with each agent by quantitating latencies to specific stages of seizures. Significant strain and sex differences were observed in sensitivity to MP-induced seizures. Rank order from least sensitive to most sensitive was C57BL, HS, DBA, and C3H. Sensitivity to flurothyl-induced seizures was also strain dependent, but the rank order of sensitivity was different than for MP. The least sensitive strain was C57BL followed by HS, C3H, and DBA. Analysis of GABA receptors in seven brain regions obtained from C57BL and DBA using 3H-muscimol to measure high affinity GABA binding did not reveal significant differences in receptor number between these two strains. It thus appears that different genetic factors influence susceptibility to MP-induced seizures than to flurothyl-induced seizures. Furthermore, there is probably little correlation between the number of high affinity GABA receptors and sensitivity to seizures.