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 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.
Celik
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Gülhane Military Medical Academy, Faculty of Medicine, Department of Pharmacology, Ankara, Turkey.
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D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*
D015259:Dopamine Agents; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001120:Arginine; D000661:Amphetamine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester