Yohimbine attenuates clonidine-induced feeding and macronutrient selection in genetically obese (ob/ob) mice.
Biochemical abnormalities in the hypothalamus of the genetically obese (C57B1/6J, ob/ob) mouse, including increased levels of endogenous norepinephrine (NE) in the paraventricular nucleus (PVN) and reduced medial hypothalamic NE metabolism, have been cited as evidence of a CNS defect contributing to altered caloric intake in this genetic strain. In the current study, the alpha 2-antagonist yohimbine (YOH) and the alpha 2-agonist clonidine (CLON) were administered systemically to 6-h meal-feeding obese and lean mice. Yohimbine (3-5 mg/kg, IP) significantly reduced total energy intake and intake of carbohydrate and fat, in both phenotypes, without altering protein intake. In contrast, CLON (25 micrograms/kg, IP) potentiated feeding, resulting in a shift in macronutrient selection toward a significant increase in the proportional intake of carbohydrate. Obese mice, however, showed an enhanced behavioral response to CLON injection. Pretreatment with 1 mg/kg YOH, a dose that alone did not significantly alter energy intake or diet selection, blocked CLON's stimulatory effect on feeding and carbohydrate preference. These results are consistent with a role for alpha 2-noradrenergic receptors in appetite regulation of ob/ob and lean mice and suggest that disturbances in this system may be involved in the development of genetic obesity.
Currie
P J
PJ
Section of Biopsychology, Clarke Institute of Psychiatry, Toronto, Ontario, Canada.
Wilson
L M
LM
D000818:Animals; D003000:Clonidine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004032:Diet; D004040:Dietary Carbohydrates / Q000494:pharmacology; D002149:Energy Intake / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects*; D005518:Food Preferences / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000523:psychology*; D015016:Yohimbine / Q000494:pharmacology*
D004040:Dietary Carbohydrates; D015016:Yohimbine; D003000:Clonidine