The corticosterone-enhancing effects of the 5-HT1A receptor antagonist, (S)-UH301, are not mediated by the 5-HT1A receptor

Eur J Pharmacol. 1995 Jan 16;272(2-3):177-83. doi: 10.1016/0014-2999(94)00645-n.

Abstract

We tried to antagonize the endocrine and behavioural changes induced by the selective 5-HT1A receptor agonist, flesinoxan, with the putative 5-HT1A receptor antagonist, (S)-UH301 ((S)-5-fluoro-8-hydroxy-2-(di-n-propylamino)tetralin). The interaction of (S)-UH301 (3 and 10 mg/kg s.c.) with flesinoxan (3 mg/kg s.c.) showed no antagonistic effects of (S)-UH301 on flesinoxan-induced corticosterone secretion. In fact, like flesinoxan (1 and 3 mg/kg s.c.), (S)-UH301 (3 and 10 mg/kg s.c.) itself dose dependently increased plasma corticosterone levels. Unlike flesinoxan, (S)-UH301 did not induce hyperglycemia, lower lip retraction and flat body posture. Moreover, flesinoxan-induced hyperglycemia and behavioural changes were effectively antagonized by (S)-UH301, showing potent 5-HT1A receptor antagonistic effects of (S)-UH301. Therefore we conclude that (S)-UH301 is a potent 5-HT1A receptor antagonist and that the (S)-UH301-induced corticosterone secretion is mediated by a non-5-HT1A receptor mechanism.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / analogs & derivatives*
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Behavior, Animal / drug effects
  • Blood Glucose / analysis
  • Corticosterone / blood*
  • Male
  • Piperazines / pharmacology
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / physiology
  • Serotonin Antagonists / pharmacology*

Substances

  • Blood Glucose
  • Piperazines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • UH 301
  • flesinoxan
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Corticosterone