The 5-HT1B receptor mediates the effect of d-fenfluramine on eating caused by intra-hypothalamic injection of neuropeptide Y.
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.
Grignaschi
G
G
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Sironi
F
F
Samanin
R
R
D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000494:pharmacology; D004347:Drug Interactions; D004435:Eating / Q000187:drug effects*; D004873:Ergolines / Q000008:administration & dosage / Q000494:pharmacology; D005277:Fenfluramine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006963:Hyperphagia / Q000139:chemically induced; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007650:Ketanserin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008711:Metergoline / Q000008:administration & dosage / Q000494:pharmacology; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects* / Q000502:physiology; D010869:Pindolol / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology
D000978:Antiparkinson Agents; D004873:Ergolines; D009478:Neuropeptide Y; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D008711:Metergoline; D005277:Fenfluramine; C047975:cyanopindolol; D007650:Ketanserin; D010869:Pindolol; C031649:mesulergine