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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Antiparkinson Agents / administration & dosage
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Antiparkinson Agents / pharmacology
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Drug Interactions
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Eating / drug effects*
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Ergolines / administration & dosage
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Ergolines / pharmacology
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Fenfluramine / administration & dosage
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Fenfluramine / antagonists & inhibitors
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Fenfluramine / pharmacology*
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Hyperphagia / chemically induced
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Hypothalamus / drug effects
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Hypothalamus / metabolism
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Injections, Intraperitoneal
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Injections, Subcutaneous
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Ketanserin / administration & dosage
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Ketanserin / pharmacology
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Male
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Metergoline / administration & dosage
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Metergoline / pharmacology
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Neuropeptide Y / administration & dosage
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Neuropeptide Y / pharmacology*
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Paraventricular Hypothalamic Nucleus / drug effects*
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Paraventricular Hypothalamic Nucleus / physiology
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Pindolol / administration & dosage
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Pindolol / analogs & derivatives
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Pindolol / pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptor, Serotonin, 5-HT1B
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Receptors, Serotonin / drug effects*
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Receptors, Serotonin / metabolism
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Serotonin Antagonists / administration & dosage
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Serotonin Antagonists / pharmacology
Substances
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Antiparkinson Agents
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Ergolines
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Neuropeptide Y
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Receptor, Serotonin, 5-HT1B
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Receptors, Serotonin
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Serotonin Antagonists
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Metergoline
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Fenfluramine
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cyanopindolol
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Ketanserin
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Pindolol
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mesulergine