CATALEPSY INDUCED BY MUSCIMOL INFUSED INTO THE HYPOTHALAMUS CAN BE SENSITIZED AND IS MODULATED BY OVARIAN-STEROIDS

Muscimol (25 ng), but not saline, infused into the region of the zona incerta and lateral hypothalamus induced significant catalepsy in fema le rats. Daily administration of muscimol for 5 days resulted in a sen sitization of the cataleptic response such that there was a significan tly greater response to the same dose of muscimol beginning on Day 3 a nd continuing to increase up to Day 5. It was determined that the incr ease in catalepsy across days was not the result of conditioning after an initial exposure to muscimol. The endocrine condition of the femal e affected the degree of catalepsy induced by the first exposure to in trahypothalamic muscimol. Ovariectomized rats pretreated with estradio l benzoate (EB) exhibited significantly greater catalepsy than did fem ales untreated or treated with progesterone or combined EB and progest erone. Weekly administration of muscimol also produced significant sen sitization of the behavioral response, and the degree of sensitization was again affected by endocrine condition. Specifically, although fem ales treated with EB for 2 days before muscimol infusion showed a sign ificantly greater catalepsy after the first infusion than did ovariect omized females, they failed to show any increase in catalepsy scores a cross the 4 weeks of treatment. The greater catalepsy induced by musci mol infusion in EB-treated females may be related to changes in dopami nergic transmission. In contrast, females pretreated with progesterone 4 hr before muscimol infusion (with or without prior EB) exhibited hi ghly significant increases in cataleptic response across the 4 weeks. Ovariectomized females receiving no hormone replacement also exhibited significant sensitization of the catalepsy across the 4 weeks, but th e response was generally weaker, with a later onset of catalepsy and a shorter duration of the muscimol effect than that seen in progesteron e-treated females. It is hypothesized that progesterone-treated animal s exhibit significantly greater degrees of sensitization of the catale ptic response because the hormone increases the efficacy of muscimol a t the GABA receptor, resulting in a higher effective dose of muscimol in these animals. The progesterone metabolite 5alpha-3alpha-dihydropre gnanolone was also found to increase the efficacy of muscimol action.