u-50488 and Obesity

We have investigated the central effect of a kappa-opioid agonist and an antagonist on the macronutrient preference in two strains of rat, the Osborne Mendel (OM) and S5B/P1 rats, that have different susceptibility to obesity and differential preference for dietary fat intake. OM rats prefer diets high in fat and are sensitive to diet-induced obesity, whereas S5B/P1 prefer a low fat diet and are resistant to high-fat diet-induced obesity. Rats adapted to a two-choice high fat (HF)/low fat (LF) diet were food deprived (20 h) and then infused into the third cerebroventricle with 10 micrograms nor-binaltorphimine (nor-BNI), a selective kappa-antagonist. Nor-BNI preferentially suppressed HF intake, but not LF intake in OM rats, whereas it affected neither diet in S5B rats. Infusion of U50488, a selective kappa-agonist (33 nmol), into the third cerebroventricle in sated rats, potently stimulated the intake of HF only in the OM rats, whereas it induced a significant but moderate stimulation of intake of both HF and LF diets in the S5B/P1 rats. Total energy intake following U50488 was not significantly different between the two strains. These findings suggest that the enhanced sensitivity of the OM rats to kappa-opioid stimulation for dietary fat may contribute to their preference for dietary fat and possibly their increased susceptibility for obesity.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics, Non-Narcotic; Animals; Behavior, Animal; Brain; Diet; Dietary Fats; Eating; Energy Metabolism; Food Preferences; Male; Naltrexone; Narcotic Antagonists; Narcotics; Obesity; Rats; Rats, Inbred Strains; Receptors, Opioid, kappa