Influence of Gender and Gonadectomy on Bicuculline-Induced Convulsions and on GABAA Receptors

Abstract

The response to IV administration of GABAA receptor antagonist bicuculline was studied in young (30 days) and in adult gonad-intact or gonadectomized male and female rats. The properties of GABAA 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 (RB 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 RB 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 3H-muscimol binding sites. In female rats, gonadectomy only decreased the affinity of cortical GABAA receptors. Only regional but not sex differences were observed in the affinity of muscimol and bicuculline for GABAA receptors. Sex differences in the threshold doses of bicuculline-producing convulsions do not correlate either with the properties of cortical and cerebellar GABAA receptors or with the affinity of bicuculline for the same binding sites.