CENTRAL SEROTONINERGIC SYSTEM INVOLVEMENT IN THE ANOREXIA INDUCED BY N-G-NITRO-L-ARGININE, AN INHIBITOR OF NITRIC-OXIDE SYNTHASE

The effects of N-G-nitro-L-arginine, an inhibitor of brain nitric oxid e (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 N-G-nitro-L-arginine ( 50 mg/kg i.p.) or repeated administration of N-G-nitro-L-arginine (50 mg/kg i.p. daily, for 7 days) reduced food intake and body weight in o bese rats. Acute administration of N-G-nitro-L-arginine reduced food i ntake in lean rats. However, lean rats showed tolerance to the N-G-nit ro-L-arginine effects after repeated administration. N-G-Nitro-L-argin ine administration significantly increased serotonin metabolism in the cortex, diencephalon and medulla-pons of obese Zucker rats after eith er acute or repeated administration of N-G-nitro-L-arginine. In contra st, N-G-nitro-L-arginine increased serotonin metabolism in lean rats o nly after acute administration, and the appearance of tolerance to N-G -nitro-L-arginine anorectic effects paralleled the failure of N-G-nitr o-L-arginine to increase serotonin metabolism. The present data extend our previous findings indicating that N-G-nitro-L-arginine possesses anorectic activity in obese Zucker rats, and clearly suggest that the central serotoninergic system mediates the anorexia induced by inhibit ors of brain NO synthase.