Bidirectional effects of clonidine on carbohydrate intake in genetically obese (ob/ob) mice.

Hypothalamic noradrenergic mechanisms contribute to altered caloric intake in genetically obese (C57BL/6J, ob/ob) mice. Noradrenergic mechanisms, principally in the paraventricular hypothalamus and of the alpha 2 subtype, have also been implicated in the macronutrient intake regulation of nonpathological models. Accordingly, this study assessed the extent to which clonidine, an alpha 2 agonist, altered macronutrient intake in genetically obese (ob/ob) and lean (C57BL/6J, +/?) mice. Following adaptation to a 6-h feeding regimen, mice were injected intraperitoneally with either clonidine (0.1, 0.5 mg/kg) or 0.15 M NaCl (Experiment 1) or 0.025 mg/kg clonidine or saline (Experiment 2) 30 min prior to simultaneous access to separate sources of carbohydrate, fat, and protein. Clonidine doses of 0.1 mg/kg or greater reduced total energy intake and intake of carbohydrate and fat (p less than 0.005) in all mice (Experiment 1). However, 0.025 mg/kg clonidine selectively increased ingestion of carbohydrate in obese mice by 212% of vehicle-injected values (p less than 0.001) without altering intake in lean mice (Experiment 2). These results implicate an alpha 2 receptor mechanism in genetic obesity.