Melanin-concentrating hormone-1 receptor antagonism decreases feeding by reducing meal size.
Prior work has demonstrated that melanin-concentrating hormone-1 (MCH-1) receptor antagonism decreases food intake and body weight in obese rodents. The purpose of this study was to determine if the MCH-1 receptor antagonist-mediated hypophagia was due a decrease in meal size, meal frequency, or both. We performed a meal pattern analysis in free-feeding hyperphagic diet-induced obese (DIO) rats treated with 1, 3 or 10 mg/kg p.o. of the MCH-1 receptor antagonist T-226296 (a (-)enantiomer of N-[6-(dimethylamino)-methyl]-5,6,7,8-tetrahydro-2-naphthalenyl]-4'-fluoro[1,1'-biphenyl]-4 carboxamide). Food intake was continuously monitored for 24 h using a BioDAQ food intake monitoring system. A total of 10 mg/kg T-226296 significantly decreased body weight and 24-h food intake, and had no effect on locomotor activity. The decrease in food intake was due to a reduction in meal size, not meal frequency. We conclude that MCH-1 receptor antagonism with T-226296 decreases food intake in DIO rats by selectively reducing meal size, and that the reduced food intake is not due to a generalized behavioral malaise.
Kowalski
Timothy J
TJ
Cardiovascular/Metabolic Disease, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. timothy.kowalski@spcorp.com
Farley
Constance
C
Cohen-Williams
Mary E
ME
Varty
Geoffrey
G
Spar
Brian D
BD
D000818:Animals; D001713:Biphenyl Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005247:Feeding Behavior / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D009765:Obesity / Q000188:drug therapy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013997:Time Factors
D001713:Biphenyl Compounds; D009281:Naphthalenes; D011979:Receptors, Pituitary Hormone; C457679:T-226296; C092274:melanin-concentrating hormone receptor