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 receptor agonist, ipsapirone (0.5 g/l in drinking water for 3 weeks), has anxiolytic activity in the rat. Herein, we investigated whether this treatment promotes tachyphylaxis to the acute neuroendocrine effects of ipsapirone. Rats chronically treated with ipsapirone displayed a 7% decrease in body weights, compared to vehicle-pretreated rats, thereby confirming previous observations. On the other hand, ipsapirone pretreatment 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 increase in plasma prolactin levels elicited by the dopaminergic receptor antagonist haloperidol. These results suggest that neither the 5-HT1A receptors nor the catecholamine receptors that mediate ipsapirone acute neuroendocrine effects develop tolerance to stimulation upon sustained ipsapirone treatment.