Nitric oxide synthase inhibitors cause motor deficits in mice

Citation
T. Araki et al., Nitric oxide synthase inhibitors cause motor deficits in mice, EUR NEUROPS, 11(2), 2001, pp. 125-133
Citations number
41
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
EUROPEAN NEUROPSYCHOPHARMACOLOGY
ISSN journal
0924-977X → ACNP
Volume
11
Issue
2
Year of publication
2001
Pages
125 - 133
Database
ISI
SICI code
0924-977X(200104)11:2<125:NOSICM>2.0.ZU;2-G
Abstract
We investigated possible motor effects of 7-nitroindazole (7-NI), an neuron al nitric oxide synthase (nNOS) inhibitor, and N-G-nitro-L-arginine methyl ester (L-NAME), an non-selective NOS inhibitor in mice using catalepsy and pole tests in comparison with dopamine D-2 receptor antagonist, haloperidol . We also studied the change in dopamine, 3,4-dihydroxyphenylacetic acid (D OPAC) and homovanillic acid (I-IVA) contents: of these compounds. The admin istration of 7-NI and L-NAME (40-160 mg/kg, s.c.) dose-dependently induced motor deficit in both catalepsy anti pole tests. The motor deficit induced by 7-NI was more pronounced than the one produced by L-NAME. In contrast, h aloperidol showed a marked motor deficit in mice. Haloperidol showed a mark ed motor deficit as compared with 7-NI and I.-NAME. For dopamine, DOPAC and HVA contents, haloperidol exhibited a significant decrease in dopamine con tent and a significant increase in DOPAC and HVA content in the striatum. I n contrast, 7-NI showed a significant increase in the striatal dopamine con tent. However, 7-N1 had no significant change in the striatal DOPAC and HVA contents. On the other hand, no significant change in the striatal dopamin e, DOPAC and HVA contents was observed in L-NAME-treated mice. The present study also showed that the motor deficit induced by 7-NI or L-NAME was sign ificantly attenuated by the treatment with L-arginine. These results demons trate that NOS inhibitors as well as dopamine D-2 receptor antagonist halop eridol can induce motor deficit in mice. The present study also suggests th at the mechanism in the motor deficit caused by NOS inhibitors may be diffe rent from that in the motor deficit induced by haloperidol. Furthermore, ou r findings suggest that nNOS may play some role in control of motor behavio r. (C) 2001 Elsevier Science B.V. All rights reserved.