Involvement of nitric oxide in phencyclidine-induced hyperlocomotion in mice

Yukihiro Noda, Kiyofumi Yamada, Hiroshi Furukawa, Toshitaka Nabeshima

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50 Citations (Scopus)


The present study was undertaken to investigate the involvement of nitric oxide (NO) in the behaviors induced by 1-(1-phenylcyclohexyl) piperidine (phencyclidine; PCP) in mice, using NG-nitro-l-arginine methyl ester (L-NAME), an inhibitor of NO synthase. PCP (1, 3, and 10 mg/kg s.c.) dose dependently induced hyperlocomotion and stereotyped behaviors, including sniffing, head movement, and ataxia, in mice. PCP also caused a marked deficit of motor coordination in mice, the effect being exerted in a dose-dependent manner. Although pretreatment with L-NAME (50 mg/kg i.p.) slightly enhanced the ataxia induced by PCP (3 mg/kg), it failed to modify other stereotyped behaviors and the lack of motor coordination induced by PCP (3 mg/kg). The hyperlocomotion induced by PCP (3 mg/kg) was significantly enhanced by L-NAME (5 and 50 mg/kg) and 7-nitro indazole (25 mg/kg), but not by D-NAME (50 mg/kg), a less active enantiomer of L-NAME. However, the behavioral changes induced by PCP, at the high dose, 10 mg/kg, were not enhanced by L-NAME and D-NAME. The enhancing effects of L-NAME on the PCP (3 mg/kg)-induced hyperlocomotion were significantly prevented by l-arginine (1 g/kg i.p.). However, d-arginine (1 g/kg i.p.) and l-lysine (1 g/kg i.p.) had no effect in this regard. These results suggested the involvement of central NO production in the mediation of PCP-induced behaviors, hyperlocomotion in particular, in mice.

Original languageEnglish
Pages (from-to)291-297
Number of pages7
JournalEuropean Journal of Pharmacology
Issue number3
Publication statusPublished - 24-11-1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pharmacology


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