A comparison of the oxytocin and vasopressin responses to the 5-HT(1A) agonist and potential anxiolytic drug alnespirone (S-20499)

Louis D. Van De Kar, Andrew D. Levy, Qian Li, Mark S. Brownfield

Research output: Contribution to journalArticle

Abstract

The effect of the serotonin(1A) (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 D2 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.

Original languageEnglish (US)
Pages (from-to)677-683
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume60
Issue number3
DOIs
StatePublished - Jun 1998
Externally publishedYes

Fingerprint

alnespirone
Serotonin Receptor Agonists
Anti-Anxiety Agents
Oxytocin
Vasopressins
Serotonin
Pharmaceutical Preparations
Receptor, Serotonin, 5-HT1A
Plasmas
Pindolol
Spiperone
Injections
Adrenergic Receptors
Rats
Reaction Time

Keywords

  • 5-HT(1A) antagonist
  • Dose-response
  • Hormone
  • Hypothalamus
  • Neuroendocrine
  • Paraventricular nucleus
  • Receptor
  • Secretion
  • Serotonin
  • Time course

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

A comparison of the oxytocin and vasopressin responses to the 5-HT(1A) agonist and potential anxiolytic drug alnespirone (S-20499). / Van De Kar, Louis D.; Levy, Andrew D.; Li, Qian; Brownfield, Mark S.

In: Pharmacology Biochemistry and Behavior, Vol. 60, No. 3, 06.1998, p. 677-683.

Research output: Contribution to journalArticle

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abstract = "The effect of the serotonin(1A) (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 D2 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.",
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