Nitric oxide synthase inhibitors cause motor deficits in mice.
We investigated possible motor effects of 7-nitroindazole (7-NI), an neuronal 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 (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 D(2) 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.
Araki
T
T
Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Science and Medicine, Aramaki, Aoba-ku, 980-8578, Sendai, Japan. tsuaraki@mail.cc.tohoku.ac.jp
Mizutani
H
H
Matsubara
M
M
Imai
Y
Y
Mizugaki
M
M
Itoyama
Y
Y
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002375:Catalepsy / Q000139:chemically induced*; D004298:Dopamine / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004409:Dyskinesia, Drug-Induced / Q000523:psychology*; D004791:Enzyme Inhibitors / Q000633:toxicity*; D006220:Haloperidol / Q000494:pharmacology; D007191:Indazoles / Q000633:toxicity; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000633:toxicity; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I
D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D007191:Indazoles; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D006220:Haloperidol; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester; D004298:Dopamine