Evidence that central 5-HT2 receptors do not play an important role in the anorectic activity of d-fenfluramine in the rat

R. Samanin, T. Mennini, C. Bendotti, D. Barone, S. Caccia, S. Garattini

Research output: Contribution to journalArticlepeer-review

Abstract

To gain information on the role of central 5-HT2 receptors in the reduction of food intake caused by d-fenfluramine in rats, different intraperitoneal doses of metergoline, a non-selective 5-HT receptor antagonist and ritanserin, a selective 5-HT2 receptor antagonist, were compared for their ability (a) to antagonize the anorectic effect of d-fenfluramine; (b) to occupy central 5-HT2 receptors in vivo (measured by the binding of [3H]spiperone in the frontal cortex) and (c) to affect the concentrations of d-fenfluramine and its active metabolite, d-norfenfluramine in brain. Metergoline dose-dependently reduced the effect of d-fenfluramine (2.5 mg/kg i.p.) on food intake, with complete antagonism at 1 mg/kg, a dose which occupies about 50% of cortical 5-HT2 receptors. Ritanserin, at a dose (0.5 mg/kg) causing 50% occupation of 5-HT2 receptors, had no effect on anorexia induced by d-fenfluramine and only partially prevented it at doses which caused maximum occupation of 5-HT2 receptors (1-2 mg/kg). Unlike 1 mg/kg metergoline, 1 mg/kg ritanserin significantly reduced the concentrations of d-norfenfluramine in the frontal cortex and hypothalamus of rats 30 min after injection of d-fenfluramine. The results suggest that 5-HT receptors, other than 5-HT2, possibly 5-HT1B, are involved in the anorectic effect of d-fenfluramine in food-deprived rats.

Original languageEnglish
Pages (from-to)465-469
Number of pages5
JournalNeuropharmacology
Volume28
Issue number5
DOIs
Publication statusPublished - 1989

Keywords

  • 5-HT receptors
  • anorexia
  • d-fenfluramine

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Drug Discovery
  • Pharmacology

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