A comparison of the oxytocin and vasopressin responses to the 5-HT1A agonist and potential anxiolytic drug alnespirone (S-20499).
The effect of the serotonin1A (5-HT1A) 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, i.p.) was as early as 15 min postinjection, with significant stimulation persisting for 30 min. Pretreatment with a low dose of the 5-HT1A/beta-adrenoceptor antagonist (-)-pindolol (0.3 mg/kg, s.c.), 30 min prior to injection of alnespirone (0, 2, 5, and 10 mg/kg, i.p.) 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-HT1A/2A/dopamine D2 antagonist spiperone (0.01 or 3 mg/kg, s.c.) 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-HT1A receptor mechanisms mediate the effect of alnespirone on the secretion of oxytocin. Furthermore, these studies suggest that 5-HT1A receptor mechanisms do not participate in the serotonergic regulation of vasopressin secretion.
Department of Pharmacology, Loyola University Chicago, Stritch School of Medicine, Maywood, IL 60153, USA.
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Van de Kar
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Levy
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Li
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Brownfield
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D010121:Oxytocin / Q000097:blood / Q000378:metabolism*; D010869:Pindolol / Q000494:pharmacology; D051381:Rats; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013134:Spiperone / Q000494:pharmacology; D013141:Spiro Compounds / Q000494:pharmacology*; D014667:Vasopressins / Q000097:blood / Q000378:metabolism*
D000319:Adrenergic beta-Antagonists; D014151:Anti-Anxiety Agents; D018492:Dopamine Antagonists; D017366:Serotonin Receptor Agonists; D013141:Spiro Compounds; D014667:Vasopressins; C075319:alnespirone; D013134:Spiperone; D010121:Oxytocin; D010869:Pindolol