Nitric oxide synthase inhibitors cause motor deficits in mice

Tsutomu Araki, Haruo Mizutani, Mitsunobu Matsubara, Yutaka Imai, Michinao Mizugaki, Yasuto Itoyama

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

Abstract

We investigated possible motor effects of 7-nitroindazole (7-NI), an neuronal nitric oxide synthase (nNOS) inhibitor, and NG-nitro-L-arginine methyl ester (L-NAME), an non-selective NOS inhibitor in mice using catalepsy and pole tests in comparison with dopamine D2 receptor antagonist, haloperidol. We also studied the change in dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) contents of these compounds. The administration of 7-NI and L-NAME (40-160 mg/kg, s.c.) dose-dependently induced motor deficit in both catalepsy and pole tests. The motor deficit induced by 7-NI was more pronounced than the one produced by L-NAME. In contrast, haloperidol showed a marked motor deficit in mice. Haloperidol showed a marked motor deficit as compared with 7-NI and L-NAME. For dopamine, DOPAC and HVA contents, haloperidol exhibited a significant decrease in dopamine content and a significant increase in DOPAC and HVA content in the striatum. In contrast, 7-NI showed a significant increase in the striatal dopamine content. However, 7-NI had no significant change in the striatal DOPAC and HVA contents. On the other hand, no significant change in the striatal dopamine, 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 significantly attenuated by the treatment with L-arginine. These results demonstrate that NOS inhibitors as well as dopamine D2 receptor antagonist haloperidol can induce motor deficit in mice. The present study also suggests that the mechanism in the motor deficit caused by NOS inhibitors may be different from that in the motor deficit induced by haloperidol. Furthermore, our findings suggest that nNOS may play some role in control of motor behavior.

Original languageEnglish
Pages (from-to)125-133
Number of pages9
JournalEuropean Neuropsychopharmacology
Volume11
Issue number2
DOIs
Publication statusPublished - 2001

Keywords

  • 7-Nitroindazole
  • Dopamine content
  • Haloperidol
  • L-NAME
  • Mice
  • Motor behavior
  • Nitric oxide synthase inhibitor

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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