Influence of gender and gonadectomy on bicuculline-induced convulsions and on GABA(A) receptors

The response to IV administration of GABA(A) receptor antagonist bicuculline was studied in young (30 days) and in adult gonad-intact or gonadectomized male and female rats, The properties of GABA(A) receptors, obtained from cortex and cerebellum 30 days following gonadectomy, and the affinity of muscimol and bicuculline for cortical and cerebellar GABA binding sites were also studied. While young rats failed to show sex differences, the threshold doses of bicuculline producing the first myoclonic twitch and running/bouncing clonus (RE clonus) were lower in adult male than female rats, Fifteen days after gonadectomy or sham operation male rats needed less bicuculline to the onset of myoclonic twitch and RE clonus than identically treated females, while orchidectomized rats needed more bicuculline to the onset of tonic hindlimb extension than all other groups examined, All sex differences disappeared 30 days following gonadectomy. At the same time, in males gonadectomy decreased the affinity and enhanced the density of cortical H-3-muscimol binding sites, In female rats, gonadectomy only decreased the affinity of cortical GABA(A) receptors, Only regional but not sex differences were observed in the affinity of muscimol and bicuculline for GABA(A) receptors. Sex differences in the threshold doses of bicuculline-producing convulsions do not correlate either with the properties of cortical and cerebellar GABA(A) receptors or with the affinity of bicuculline for the same binding sites. (C) 1997 Elsevier Science Inc.