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

Abstract

Effects of N G-nitroarginine methyl ester ( l-NAME), a nonspecific inhibitor of nitric oxide (NO) synthase, on amphetamine-induced locomotor activity were investigated in Swiss–Webster mice. Locomotor activity was measured for 30 min immediately following amphetamine (1, 2 and 4 mg/kg, i.p.) or saline treatments. l-NAME (15 and 30 mg/kg) and a combination of l-arginine (1000 mg/kg) and l-NAME (30 mg/kg) were injected 30 min before amphetamine (2 mg/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 (1000 mg/kg) were also tested for ability to depress or stimulate locomotor activity 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 prevented the inhibitory effects of l-NAME on amphetamine-induced locomotor stimulation. l-NAME and l-arginine did not cause any significant change in locomotor activity in mice not treated with amphetamine. These results suggest that amphetamine-induced locomotor stimulation in mice is modulated by NO.