Evidence that nitric oxide stimulates feeding in the marsupial Sminthopsis crassicaudata

Nitric oxide (NO) synthase inhibitors reduce food intake in rodents and chickens, suggesting that NO may stimulate feeding. We used two competitive, non-selective inhibitors of NO synthase (NOS), (NG-monomethyl-L-arginine ester [L-NMMA] and NG-nitro-L-arginine methyl ester [L-NAME]), to evaluate the role of NO mechanisms in the control of food intake in a marsupial model previously used in studies of appetite regulation. Adult male Sminthopsis crassicaudata (n = 11-16, 15 +/- 0.3 g, mean +/- S.E.M.) received L-NMMA (50, 100, 200 and 1000 mg/kg), L-NAME (50, 100 and 200 mg/kg), L-arginine (L-arg) the precursor of NO (1000 and 2000 mg/kg), L-NAME (200 mg/kg) in combination with L-arg (2000 mg/kg), or saline (0.9%). All drugs were administered intraperitoneally after 24 h of food deprivation, after which food was immediately made available ad libitum. Food intake was measured 0, 0.5, 1, 2, 4 and 24 h after treatments. In addition, we studied the effect of acute L-NAME administration on hypothalamic, cortical, hepatic and cardiac NOS activity by quantifying citrulline production. L-NMMA (1000 mg/kg) and L-NAME (100 and 200 mg/kg) suppressed food intake by 25%, 21%, and 30%, respectively, over 24 h after treatments (P < 0.05). L-arg (1000 and 2000 mg/kg) by itself had no significant effect on food intake when compared with saline (P > 0.05). When administered in combination with L-NAME (200 mg/kg), L-arg (2000 mg/kg) reversed L-NAME induced suppression of appetite (P> 0.05). Furthermore, L-NAME (200 mg/kg) significantly decreased hypothalamic (P < 0.01), cortical (P < 0.01) and hepatic (P < 0.03) NOS activity. L-NAME had no effect on cardiac NOS activity (P> 0.05). These data show that peripheral administration of L-NAME has a significant central effect, particularly in brain areas involved in appetite regulation, and suggest in marsupials, as in other mammals and birds, that NO plays a role in the regulation of food intake.