DO NMDA RECEPTOR-MEDIATED CHANGES IN MOTOR BEHAVIOR INVOLVE NITRIC-OXIDE

Nitric oxide (NO) synthase inhibitors were investigated for their effects on motor behaviour. In normal mice, N-G-nitro-L-arginine (5-125 mg/kg i.p.) and 7-nitroindazole (10-50 mg/kg i.p.), but not aminoguanidine (60-150 mg/kg i.p.) suppressed species-typical behaviours. In 24 h reserpine-treated mice, akinesia was reversed with the dopamine D-1 receptor agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine hydrochloride (SKF 38393, 3-30 mg/kg i.p.) and by the dopamine D-2 receptor agonist N-n-propyl-N-phenylethyl-p-(3-hydroxyethyl) ethylamine hydrochloride (RU 24213, 0.5-5 mg/kg s.c.), but not by any of the NO synthase inhibitors. N-G-Nitro-L-arginine and 7-nitroindazole (not aminoguanidine) suppressed D-1 and D-2 receptor agonist-induced locomotion, but L-arginine (500 mg/kg i.p.) was not always able to prevent this effect. These results suggest that continued activity of constitutive NO synthase is necessary for normal body movements to occur. The difference in the interaction profiles of constitutive NO synthase inhibitors and NMDA antagonists with dopaminergic drugs, indicates that inhibition of NO generation is not a factor in the well-known D-1-facilitatory effect of glutamate receptor blockade.