CHRONIC TREATMENT WITH AN ANXIOLYTIC DOSE OF THE 5-HT(1A) AGONIST IPSAPIRONE DOES NOT ALTER IPSAPIRONE ACUTE NEUROENDOCRINE EFFECTS

We recently reported that chronic administration of the 5-HT1A recepto r agonist, ipsapirone (0.5 g/l in drinking water for 3 weeks), has anx iolytic activity in the rat. Herein, we investigated whether this trea tment promotes tachyphylaxis to the acute neuroendocrine effects of ip sapirone. Rats chronically treated with ipsapirone displayed a 7% decr ease in body weights, compared to vehicle-pretreated rats, thereby con firming previous observations. On the other hand, ipsapirone pretreatm ent did not affect basal plasma levels of adrenocorticotropin (ACTH), corticosterone, prolactin, aldosterone, and renin activity, nor did it affect their respective rises following an acute ipsapirone (50 mg/kg PO) challenge. Moreover, ipsapirone pretreatment did not affect the i ncrease in plasma prolactin levels elicited by the dopaminergic recept or antagonist haloperidol. These results suggest that neither the 5-HT 1A receptors nor the catecholamine receptors that mediate ipsapirone a cute neuroendocrine effects develop tolerance to stimulation upon sust ained ipsapirone treatment.