Central serotoninergic system involvement in the anorexia induced by NG-nitro-L-arginine, an inhibitor of nitric oxide synthase.
The effects of NG-nitro-L-arginine, an inhibitor of brain nitric oxide (NO) synthase, on central serotoninergic system were studied in male obese Zucker rats and in their lean age-matched controls (FA/?; FA/FA), both groups aged 14 weeks. Acute injection of NG-nitro-L-arginine (50 mg/kg i.p.) or repeated administration of NG-nitro-L-arginine (50 mg/kg i.p. daily, for 7 days) reduced food intake and body weight in obese rats. Acute administration of NG-nitro-L-arginine reduced food intake in lean rats. However, lean rats showed tolerance to the NG-nitro-L-arginine effects after repeated administration. NG-Nitro-L-arginine administration significantly increased serotonin metabolism in the cortex, diencephalon and medulla-pons of obese Zucker rats after either acute or repeated administration of NG-nitro-L-arginine. In contrast, NG-nitro-L-arginine increased serotonin metabolism in lean rats only after acute administration, and the appearance of tolerance to NG-nitro-L-arginine anorectic effects paralleled the failure of NG-nitro-L-arginine to increase serotonin metabolism. The present data extend our previous findings indicating that NG-nitro-L-arginine possesses anorectic activity in obese Zucker rats, and clearly suggest that the central serotoninergic system mediates the anorexia induced by inhibitors of brain NO synthase.
Squadrito
F
F
Department of Internal Medicine, School of Medicine, University of Messina, Italy.
Calapai
G
G
Altavilla
D
D
Cucinotta
D
D
Zingarelli
B
B
Arcoraci
V
V
Campo
G M
GM
Caputi
A P
AP
D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004435:Eating / Q000187:drug effects; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D009765:Obesity / Q000235:genetics / Q000523:psychology; D051381:Rats; D011924:Rats, Zucker; D012701:Serotonin / Q000378:metabolism / Q000502:physiology*; D014364:Tryptophan / Q000378:metabolism
D001067:Appetite Depressants; D019335:Nitroarginine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D014364:Tryptophan; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases