Are 5-HT_1A Autoreceptors Involved in the Inhibitory Effect of Ipsapirone on Cold-Elicited Thyrotropin Secretion?

Abstract

Administration of the serotonin (5-HT)_1a receptor agonist ipsapirone has been shown to decrease cold-elicited thyrotropin (TSH) secretion. We have analyzed (1) the influence of 5-HT_1a receptors and ipsapirone metabolism into 1-(2-pyrimidinyl)-piperazine (1-PP, an α₂-adrenoceptor antagonist) on the effect of ipsapirone on TSH release, and (2) the interaction between the corticosterone-releasing effect of ipsapirone and its inhibitory influence on TSH release. Pretreatment with proadifen (50 mg/kg, 5 h before ipsapirone), i.e. an inhibitor of ipsapirone metabolism into 1-PP, did not affect ipsapirone-induced inhibition of 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-HT_1A receptor blocker (–)-pindolol (5 mg/kg) increased baseline and cold-elicited TSH release but the inhibitory influence of ipsapirone on cold-elicited TSH release was alleviated by (–)-pindolol pretreatment only. Cold exposure increased corticosterone release, an effect which was insensitive to (–)-pindolol pretreatment. Lastly, pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine prevented the immediate inhibitory effect of the selective 5-HT_1a receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) upon cold-induced TSH release, but it amplified the late release of TSH in cold-exposed 8-OH-DPAT-injected rats. These results suggest that presynaptic 5-HT_1a receptors mediate ipsapirone-induced inhibition of cold-elicited TSH release, an effect which may be partially opposed by postsynaptic 5-HT_1a receptor stimulation.

Neuroendocrine and Autonomous Mechanisms Underlying Thermoregulation in Cold Environment

“…Another possiblity could be the existence of inhibitory influences of the PVN on raphe TRH neurons, but anatomical connections between PVN and raphe nucleus have not been identified so far. In contrast, raphe fibers impinge on PVN through serotonin (5-HT) inner vation [16] and 5-HT drugs acting on the raphe exihibit both thermoregulatory and neuroendocrine effects under cold exposure [17,18].…”

“…A central, inhibitory effect of the serotoninergic ago nist ipsapirone on both cold-induced TSH [18] and TRH [17] release has been observed. Ipsapirone is a well-known presynaptic 5-HT|A autoreceptor agonist: its administra tion inhibits endogenous serotoninergic transmission, and is antagonized by pindolol, a 5-HT|A receptor antago nist [ 18].…”

“…Ipsapirone is a well-known presynaptic 5-HT|A autoreceptor agonist: its administra tion inhibits endogenous serotoninergic transmission, and is antagonized by pindolol, a 5-HT|A receptor antago nist [ 18]. Thus, a new explanation of 5-HT stimulation of TSH secretion under cold exposure could involve presyn aptic serotoninergic receptors.…”

Gender-dependent dissociation between oxytocin but not ACTH, cortisol or TSH responses to m -chlorophenylpiperazine in healthy subjects

“…There is evidence that central 5-HT input interferes with TSH secretion through complex central mechanisms (Toivonen and Mannistö 1990). Stimulation of presynaptic 5-HT 1A receptors causes a decrease in cold-induced TSH secretion and this e¤ect may be partly opposed by postsynaptic 5-HT 1A receptor stimulation (Broqua et al 1993). m-CPP increases body temperature in humans and rats (Murphy et al 1991).…”