Potentiation of dark onset feeding in obese mice (genotype ob/ob) following central injection of norepinephrine and clonidine.
Central monoaminergic neurotransmitters have been implicated in the control of food intake in different animal species but it remains unclear whether these same neurochemical systems effectively regulate feeding behaviour in the genetically obese (ob/ob) mouse. Neuropharmacological studies have demonstrated, for example, that microinjection of norepinephrine can elicit a reliable feeding response in the rat, particularly at dark onset. The present study was therefore designed to examine the impact of central injection of norepinephrine (20-160 nmol) and clonidine (5-80 nmol), an alpha 2-adrenoceptor agonist, on food intake in ob/ob mice and lean (+/?) controls. Presatiated obese and lean mice were injected with norepinephrine or clonidine immediately prior to the onset of the dark cycle. Food intake (kcal) was measured 1 h postinjection. Obese mice ingested more food than lean mice under baseline saline conditions. Injection of norepinephrine and clonidine increased eating in both phenotypes, although the ob/ob showed an enhanced feeding response to norepinephrine and clonidine administration. Intracerebroventricular pretreatment with the alpha 2-adrenoceptor antagonist yohimbine (12.5-50 nmol) significantly attenuated the increase in food intake observed in response to central injection of norepinephrine (40 nmol) and clonidine (10 nmol). However, the alpha 1-adrenoceptor antagonist corynanthine (15-60 nmol) or the beta-adrenoceptor antagonist propranolol (25-100 nmol) failed to alter noradrenergic feeding. These results suggest that modification of central alpha 2-noradrenergic function can alter natural feeding in mice, and that the ob/ob is particularly sensitive to this effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Currie
P J
PJ
Clarke Institute of Psychiatry, University of Toronto, Canada.
Wilson
L M
LM
D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003624:Darkness; D005247:Feeding Behavior / Q000187:drug effects*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009638:Norepinephrine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010641:Phenotype; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology; D013238:Stereotaxic Techniques; D015016:Yohimbine / Q000008:administration & dosage / Q000494:pharmacology
D015016:Yohimbine; D011433:Propranolol; D003000:Clonidine; D009638:Norepinephrine