Nitric oxide synthase inhibition blocks amphetamine-induced locomotor activity in mice

Effects of N-G-nitroarginine methyl ester (L-NAME), a nonspecific inhibitor of nitric oxide (NO) synthase, on amphetamine-induced locomotor activity w ere investigated in Swiss-Webster mice. Locomotor activity was measured for 30 min immediately following amphetamine (1, 2 and 4 mg/kg, i.p.) or salin e treatments. L-NAME (15 and 30 mg/kg) and a combination of L-arginine (100 0 mg/kg) and L-NAME (30 mg/kg) were injected 30 min before amphetamine (2 m g/kg) to other groups of the mice. L-Arginine was injected 30 min before L- NAME treatment when they were combined. L-NAME (30 mg/kg) and L-arginine (1 000 mg/kg) were also tested for ability to depress or stimulate locomotor a ctivity in the absence of amphetamine. Amphetamine caused a dose-dependent increase in locomotor activity of the mice. L-NAME blocked the amphetamine- induced locomotor stimulation dose dependently. L-Arginine pretreatment pre vented the inhibitory effects of L-NAME on amphetamine-induced locomotor st imulation. L-NAME and L-arginine did not cause any significant change in lo comotor activity in mice not treated with amphetamine. These results sugges t that amphetamine-induced locomotor stimulation in mice is modulated by NO . (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.