A nitric oxide synthase inhibitor, L-NAME, attenuates saccharin drinking in a two-choice test in water-deprived rats

The nitric oxide synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) [0 (veh)], 10, 25, and 50 mg/kg s.c.) was administered to water-deprived, saccharin-preferring, rats in a 30-min two-bottle choice test of 0.1% sodium saccharin and tap water in a within subjects design. Saccharin intake was selectively attenuated in a dose-related manner with increasing dose of L-NAME, reaching statistical significance at 25 and 50 mg/kg L-NAME when compared to vehicle control condition (p < 0.01). In contrast, water intake was not appreciably affected. Total fluid intake was attenuated as well. Neither saccharin nor water intake in a second group of animals was significantly affected by the inactive isomer, D-NAME, suggesting a stereospecific action. These data suggest that a taste factor might contribute to the well-documented hypophagic action of NOS inhibitors in a number of animal species. The possibility that such effect might be mediated through a serotonergic mechanism is considered.