INVOLVEMENT OF NITRIC-OXIDE IN PHENCYCLIDINE-INDUCED HYPERLOCOMOTION IN MICE

The present study was undertaken to investigate the involvement of nit ric oxide (NO) in the behaviors induced by 1-(1-phenylcyclohexyl) pipe ridine (phencyclidine; PCP) in mice, using N-G-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 behavio rs, including sniffing, head movement, and ataxia, in mice. PCP also c aused 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 moto r coordination induced by PCP (3 mg/kg). The hyperlocomotion induced b y 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 b y PCP, at the high dose, 10 mg/kg, were not enhanced by L-NAME and D-N AME. The enhancing effects of L-NAME on the PCP (3 mg/kg)-induced hype rlocomotion 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 ef fect in this regard. These results suggested the involvement of centra l NO production in the mediation of POP-induced behaviors, hyperlocomo tion in particular, in mice.