A nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester, attenuates lipoprivic feeding in mice.

Possible involvement of nitric oxide (NO) in lipoprivic feeding was investigated in nondeprived male ICR mice adapted to a high-fat diet in a within-subjects design. Lipoprivation was induced by blocking fatty acid oxidation with Na-mercaptoacetate (MA), which produces a short-term increase in feeding in mice and rats. Food intake, measured at 1, 2, and 4 h following injection of 70 mg/kg of MA, was attenuated in a dose related manner with increasing pretreatment dose (1,10, 25 and 50 mg/kg sc) of the NO-synthase (NOS) inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), reaching statistical significance at 10 mg/kg of L-NAME at h1 when compared to vehicle control condition. The inactive isomer, D-NAME, was ineffective, thereby supporting stereospecific drug action and directly implicating NO. A control experiment measured general locomotor activity (grid crossings and rears) in an open arena under 10-50 mg/kg of L-NAME in the same mice; both measures were significantly different from vehicle condition only at the highest dose. These findings support involvement of NO in lipoprivic hyperphagia; they are consistent with and extend research linking NO and ingestive behaviors through use of NOS inhibitors. Possible influences of confounds were discussed.