Parabrachial infusion of D-fenfluramine reduces food intake. Blockade by the 5-HT(1B) antagonist SB-216641.
Systemic administration of the serotonin (5-HT) releaser/reuptake inhibitor, D-fenfluramine decreases consumption of food in mammals. This hypophagic action involves loci at several levels of the neuraxis. Indirect evidence implicates the parabrachial nucleus (PBN) of the pons as one of these regions. Consistent with this hypothesis, unilateral infusion of D-fenfluramine (200, 280, and 400 nmol/0.5 microl) directly into the lateral PBN (LPBN) of male rats reduced food intake by 33%, 56%, and 66% from baseline (7.3 +/- 0.7 g) during a 30-min test with chow. Infusions lateral, medial, and dorsal to the PBN were ineffective. Stimulating 5-HT(1B) receptors in the PBN also reduces feeding. Administration of the selective 5-HT(1B) agonist CP-93,129 (3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one) (0, 0.625, 2.5, and 10 nmol/0.5 microl) into the PBN reduced food intake by 25--79%. The selective 5-HT(1B) antagonist SB-216641 (N-[3-[3-(dimethylamino(ethoxy]-4-methoxyphenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-carboxamide) (2.5 nmol) completely blocked the hypophagic action of the approximate ED(50) doses of CP-93,129 (2.5 nmol) and D-fenfluramine (280 nmol). These data strongly suggest that directly or indirectly activating 5-HT(1B) receptors in the LPBN inhibits feeding and implicates this pontine region in the serotonergic regulation of eating and satiation.
Simansky
Kenny J
KJ
Department of Pharmacology and Physiology, MCP Hahnemann University, Mailstop 488, NCB 8808, Philadelphia, PA 19102, USA. simansky@drexel.edu
Nicklous
Danielle M
DM
D000818:Animals; D001549:Benzamides / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D001917:Brachial Plexus; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005277:Fenfluramine / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D010069:Oxadiazoles / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
D001549:Benzamides; D005277:Fenfluramine; D010069:Oxadiazoles; D011725:Pyridines; D011758:Pyrroles; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C108531:N-(3-(2-dimethylamino)ethoxy-4-methoxyphenyl)-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one