Nitric oxide mediates hyperphagia of obese Zucker rats: relation to specific changes in the microstructure of feeding behavior.
The presence of a nitric oxide synthetase (NOS) was demonstrated in the rat brain. It has been demonstrated recently that NOS-inhibitors reduce food intake in mammals and this suggest that nitric oxide (NO) might be a physiological mediator involved in the mechanisms controlling feeding behavior. Actually, there is no information about the acute central and peripheral effects of NOS-inhibitors on feeding behavior in obese and lean Zucker rats. That is why we investigated the acute dose-dependent activity of NG-Nitro-Arginine-Methyl-Ester (L-NAME) on food intake and feeding behavior in these rats. When given peripherally in the obese rats, L-NAME produced a dose-dependent decrease in food intake (p<0.001). The calculated MED and the ED 50 were 0.50 mg/kg IP and 3.46 mg/kg IP, respectively. These effects could not be reproduced in the lean Zucker rats whatever the dose used (p=0.59). The anorectic properties of L-NAME were very well translated into the microstructure of the feeding behavior. Time spent to eat (p<0.001), meal duration (p<0.01) and meal number (p<0.01) were reduced in the obese rats. Interestingly, L-NAME produced the same effects in the lean rats, but meal size increased in a compensatory manner. Central administration of L-NAME reproduced the same effects in the obese rats, but lean rats still remained insensitive. Central aminergic and/or peptidergic defects associated with the expression of hyperphagia might explain the differences observed between these lean and the obese animals. These results indicate a role of nitric oxide in the expression of hyperphagia and show that it might be a physiological mediator involved in the mechanisms controlling feeding behavior.
Stricker-Krongrad
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A
INSERM U-308. MRCA. Equipe de Neurobiologie et Physiologie Expérimentales, Nancy, France. stricker@u308.inserm.nancy.fr
Beck
B
B
Burlet
C
C
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001835:Body Weight / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D006963:Hyperphagia / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009765:Obesity / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D051381:Rats; D011924:Rats, Zucker
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester