Do NMDA receptor-mediated changes in motor behaviour involve nitric oxide?
Nitric oxide (NO) synthase inhibitors were investigated for their effects on motor behaviour. In normal mice, NG-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 D1 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 D2 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. NG-Nitro-L-arginine and 7-nitroindazole (not aminoguanidine) suppressed D1 and D2 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 D1-facilitatory effect of glutamate receptor blockade.
Starr
M S
MS
Department of Pharmacology, School of Pharmacy, London, UK.
Starr
B S
BS
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine; D010627:Phenethylamines / Q000494:pharmacology; D017447:Receptors, Dopamine D1 / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology
D010627:Phenethylamines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D019335:Nitroarginine; D009569:Nitric Oxide; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride; D012110:Reserpine; D001120:Arginine