ARE 5-HT1A AUTORECEPTORS INVOLVED IN THE INHIBITORY EFFECT OF IPSAPIRONE ON COLD-ELICITED THYROTROPIN SECRETION

Administration of the serotonin (5-HT)1A receptor agonist ipsapirone h as been shown to decrease cold-elicited thyrotropin (TSH) secretion. W e have analyzed (1) the influence of 5-HT1A receptors and ipsapirone m etabolism into 1-(2-pyrimidinyl)-piperazine (I-PP, an alpha2-adrenocep tor antagonist) on the effect of ipsapirone on TSH release, and (2) th e interaction between the corticosterone-releasing effect of ipsapiron e and its inhibitory influence on TSH release. Pretreatment with proad ifen (50 mg/kg, 5 h before ipsapirone), i.e. an inhibitor of ipsapiron e metabolism into 1-PP, did not affect ipsapirone-induced inhibition o f cold-elicited TSH secretion. Pretreatment (15 min before ipsapirone) with the 5-HT1/5-HT2 receptor antagonist metergoline 2 mg/kg) or with the 5-HT1A receptor blocker (-)-pindolol (5 mg/kg) increased baseline and cold-elicited TSH release but the inhibitory influence of ipsapir one on cold-elicited TSH release was alleviated by (-)-pindolol pretre atment only. Cold exposure increased corticosterone release, an effect which was insensitive to (-)-pindolol pretreatment. Lastly, pretreatm ent with the 5-HT synthesis inhibitor p-chlorophenylalanine prevented the immediate inhibitory effect of the selective 5-HT1A receptor agoni st 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) upon cold-induce d TSH release, but it amplified the late release of TSH in cold-expose d 8-OH-DPAT-injected rats. These results suggest that presynaptic 5-HT 1A receptors mediate ipsapirone-induced inhibition of cold-elicited TS H release, an effect which may be partially opposed by postsynaptic 5- HT1A receptor stimulation.