5-Hydroxytryptamine1A receptor-mediated effects of buspirone, gepirone and ipsapirone

The effects of the nonbenzodiazepine anxiolytic agents, buspirone, gepirone and ipsapirone on body temperature and corticosterone secretion were studied in the rat. The administration of buspirone, gepirone and ipsapirone resulted in dose-related decreases in body temperature and increases in the plasma concentration of corticosterone. Spiperone produced a dose-related inhibition of the hypothermic and corticosterone responses to gepirone. Spiperone also inhibited ipsapirone-induced changes in body temperature and hormone secretion. Although spiperone also blocked the buspirone-induced stimulation of corticosterone, it did not attenuate the hypothermic response to buspirone at the dose tested. (-)-Pindolol, a potent 5-HT1A antagonist, prevented gepirone- and ipsapirone-induced hypothermia and corticosterone secretion. (-)-Pindolol also blocked the hypothermic but not the corticosterone response to buspirone. Ketanserin, a 5-HT2 antagonist, did not inhibit the hypothermic or corticosterone responses produced by these novel anxiolytic agents. It is concluded that buspirone, gepirone and ipsapirone produce hypothermia and increase plasma concentrations of corticosterone by activating 5-HT1A receptor mechanisms.