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The 5-HT1B receptor mediates the effect of d-fenfluramine on eating caused by intra-hypothalamic injection of neuropeptide Y.

Abstract
d-Fenfluramine (0.63 mg/kg i.p.), a serotonin (5-hydroxytryptamine, 5-HT) releaser and re-uptake inhibitor, reduced the eating caused by neuropeptide Y (235 pmol) injected into the paraventricular nucleus of the hypothalamus. The 5-HT1 and 5-HT2 receptor antagonist metergoline (1.0 and 2.0 mg/kg i.p.) and the 5-HT1A and 5-HT1B receptor antagonist (+/-)-cyanopindolol (3.0 and 8.0 mg/kg s.c.) significantly antagonized the effect of d-fenfluramine. The 5-HT2A and 5-HT2C receptor antagonist mesulergine (0.1 and 0.3 mg/kg s.c.) and the 5-HT2A receptor antagonist ketanserin (2.5 and 5.0 mg/kg i.p.) did not significantly modify the effect, nor did the 5-HT1A and 5-HT1B receptor antagonist (-)-propranolol (20-40 nmol), injected bilaterally into the paraventricular nucleus of the hypothalamus. The results suggest that d-fenfluramine reduces neuropeptide Y's hyperphagia by indirectly stimulating 5-HT1B receptors outside the paraventricular nucleus of the hypothalamus.
AuthorsG Grignaschi, F Sironi, R Samanin
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 274 Issue 1-3 Pg. 221-4 (Feb 14 1995) ISSN: 0014-2999 [Print] Netherlands
PMID7768274 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antiparkinson Agents
  • Ergolines
  • Neuropeptide Y
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Metergoline
  • Fenfluramine
  • cyanopindolol
  • Ketanserin
  • Pindolol
  • mesulergine
Topics
  • Analysis of Variance
  • Animals
  • Antiparkinson Agents (administration & dosage, pharmacology)
  • Drug Interactions
  • Eating (drug effects)
  • Ergolines (administration & dosage, pharmacology)
  • Fenfluramine (administration & dosage, antagonists & inhibitors, pharmacology)
  • Hyperphagia (chemically induced)
  • Hypothalamus (drug effects, metabolism)
  • Injections, Intraperitoneal
  • Injections, Subcutaneous
  • Ketanserin (administration & dosage, pharmacology)
  • Male
  • Metergoline (administration & dosage, pharmacology)
  • Neuropeptide Y (administration & dosage, pharmacology)
  • Paraventricular Hypothalamic Nucleus (drug effects, physiology)
  • Pindolol (administration & dosage, analogs & derivatives, pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Serotonin, 5-HT1B
  • Receptors, Serotonin (drug effects, metabolism)
  • Serotonin Antagonists (administration & dosage, pharmacology)

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