title: The inhibitory effect of combination treatment with leptin and cannabinoid CB1 receptor agonist on food intake and body weight gain is mediated by serotonin 1B and 2C receptors.
abstract: Previous studies reported that the co-injection of leptin and cannabinoid CB1 receptor antagonists reduces food intake and body weight in rats, and this effect is more profound than that induced by these compounds individually. Additionally, serotonin mediates the effects of numerous anorectic drugs. To investigate whether serotonin interacts with leptin and endocannabinoids to affect food intake and body weight, we administered 5-hydroxytryptamine(HT)1B and 5-hydroxytryptamine(HT)2C serotonin receptor antagonists (3 mg/kg GR 127935 and 0.5 mg/kg SB 242084, respectively) to male Wistar rats treated simultaneously with leptin (100 μg/kg) and the CB1 receptor inverse agonist AM 251 (1 mg/kg) for 3 days. In accordance with previous findings, the co-injection of leptin and AM 251, but not the individual injection of each drug, resulted in a significant decrease in food intake and body weight gain. Blockade of the 5-HT1B and 5-HT2C receptors completely abolished the leptin- and AM 251-induced anorectic and body-weight-reducing effects. These results suggest that serotonin mediates the leptin- and AM 251-dependent regulation of feeding behavior in rats via the 5-HT1B and 5-HT2C receptors.
authors: Department of Behavioral Pathophysiology, Institute of General and Experimental Pathology, Medical University of Lodz, Lodz, Poland. ewa.bojanowska@umed.lodz.pl.
authors: M
authors: M
authors: Wierucka-Rybak
authors: Department of Behavioral Pathophysiology, Institute of General and Experimental Pathology, Medical University of Lodz, Lodz, Poland.
authors: M
authors: M
authors: Wolak
authors: Department of Pathophysiology and Experimental Neuroendocrinology, Institute of General and Experimental Pathology, Medical University of Lodz, Lodz, Poland.
authors: M
authors: M
authors: Juszczak
authors: Department of Neuropeptide Research, Institute of General and Experimental Pathology, Medical University of Lodz, Lodz, Poland.
authors: J
authors: J
authors: Drobnik
authors: Department of Behavioral Pathophysiology, Institute of General and Experimental Pathology, Medical University of Lodz, Lodz, Poland.
authors: E
authors: E
authors: Bojanowska
mesh_terms: D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D004357:Drug Synergism; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D007211:Indoles / Q000494:pharmacology; D020738:Leptin / Q000494:pharmacology*; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
chemical_list: C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D063386:Cannabinoid Receptor Agonists; D007211:Indoles; D020738:Leptin; D010069:Oxadiazoles; D010879:Piperazines; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D044302:Receptor, Serotonin, 5-HT1B; D044405:Receptor, Serotonin, 5-HT2C; D058829:Serotonin 5-HT1 Receptor Antagonists; D058830:Serotonin 5-HT2 Receptor Antagonists; C090701:GR 127935; C103505:AM 251