γ‐Aminobutyric Acid and Benzodiazepine Binding Sites in Audiogenic Seizure‐Susceptible Mice

Abstract

The properties of .gamma.-GABA recognition sites, benzodiazepine binding sites and the effect of exogenous GABA on benzodiazepine binding were determined in crude membrane fractions prepared from the brains of DBA/2 mice at ages before (8-9 and 17-18 days), during (22-23 and 28-29 days) and after (40-43 days) the age of high susceptibility to audiogenic seizures. These were compared with data from age-matched mice of a strain (TO) with lower audiogenic seizure susceptibility. The number of high-affinity [3H]GABA binding sites was lower at all ages in DBA/2 mice compared with TO mice, but the affinity was higher in DBA/2 mice. The number of low-affinity [3H]GABA binding sites was lower at 8-9 days and 40-43 days in DBA/2 mice but was not significantly different from TO mice at other ages. For [3H]flunitrazepam binding, the only difference found was a slight reduction in the number of binding sites at 28-29 days of age in DBA/2 mice. GABA stimulation of [3H]flunitrazepam binding was not significantly different up to 22-23 days of age but was higher in DBA/2 mice at 28-29 days and lower at 40-43 days. Impairment of GABA function is a possible permissive factor in the age-dependent audiogenic seizure susceptibility in DBA/2 mice.