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.
Currie
P J
PJ
Department of Psychology, University of Manitoba, Winnipeg, Canada.
Wilson
L M
LM
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003000:Clonidine / Q000494:pharmacology*; D004032:Diet; D004040:Dietary Carbohydrates; D004041:Dietary Fats / Q000494:pharmacology; D004044:Dietary Proteins / Q000494:pharmacology; D002149:Energy Intake / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000523:psychology*; D010641:Phenotype
D004040:Dietary Carbohydrates; D004041:Dietary Fats; D004044:Dietary Proteins; D003000:Clonidine