A Comparison of the Oxytocin and Vasopressin Responses to the 5-HT 1A Agonist and Potential Anxiolytic Drug Alnespirone (S-20499)

Abstract

VAN DE KAR, L. D., A. D. LEVY, Q. LI AND M. S. BROWNFIELD. A comparison of the oxytocin and vasopressin responses to the 5-HT 1 A agonist and potential anxiolytic drug alnespirone (S-20499). PHARMACOL BIOCHEM BEHAV 60(3) 677–683, 1998.—The effect of the serotonin1A (5-HT 1A) agonist alnespirone (S-20499) on the secretion of both oxytocin and vasopressin was examined in the same conscious, unrestrained male rats. The dose–response and time–course effects on the secretion of oxytocin and vasopressin revealed that alnespirone stimulated oxytocin in a dose-dependent manner, but did not increase vasopressin secretion. Time of maximal effect following injection of alnespirone (5 mg/kg, IP) was as early as 15 min postinjection, with significant stimulation persisting for 30 min. Pretreatment with a low dose of the 5-HT 1A/ β-adrenoceptor antagonist ( −)-pindolol (0.3 mg/kg, SC), 30 min prior to injection of alnespirone (0, 2, 5, and 10 mg/kg, IP) shifted the dose–response curve to the right and inhibited the effect of alnespirone on plasma oxytocin concentration. Furthermore, pretreatment with a low or a high dose of the 5-HT 1A/2A/dopamine D 2 antagonist spiperone (0.01 or 3 mg/kg, SC) dose dependently shifted the alnespirone dose–response curve effect of alnespirone to the right. None of these drugs, alone or in combination, altered plasma vasopressin levels. These studies suggest that 5-HT 1A receptor mechanisms mediate the effect of alnespirone on the secretion of oxytocin. Furthermore, these studies suggest that 5-HT 1A receptor mechanisms do not participate in the serotonergic regulation of vasopressin secretion.