Enhancement of caffeine-induced locomotor hyperactivity produced by the combination with L-arginine or taurine in mice: Possible involvement of nitric oxide.

Combinations of caffeine with L-arginine or with taurine can enhance the effect of caffeine, but the mechanisms remain elusive. This study was designed to test the hypothesis that stimulant effects of central nervous system nitric oxide (NO) may explain the beneficial effect of caffeine on combinations with amino acid, L-arginine or taurine. Caffeine increased the spontaneous locomotor activity dose-dependently (2-10 mg/kg) in mice. The locomotor activity induced by caffeine at a dose of 2 mg/kg was enhanced by combined administration of L-arginine at a dose of 600 mg/kg, or taurine at a dose of 400 mg/kg, respectively. For both combinations, enhancement was significantly inhibited by pretreatment with N-nitro-L-arginine methyl ester (L-NAME) at a dose of 40 mg/kg. These results suggest that the enhancement induced by combining caffeine with amino acid might be regulated at least in part by NO in the central nervous system.