Effects of nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester on phencyclidine-induced effects in rats

Phencyclidine (PCP) is widely used as an animal model of schizophrenia. In rats, acute PCP treatment increased locomotor activity and induced stereoty ped behaviours consisting of head weaving, turning and backpedalling. PCP h ad differential regional effects on c-Sos expression in rat brain, suggesti ng different patterns of neuronal activity. The most prominent immunostaini ng was observed in the cortical regions. To elucidate the role of nitric ox ide, an important intracellular messenger, in the mechanism of action of PC P the effects of nitric oxide synthase inhibitor N-G-nitro-L-arginine methy l ester (L-NAME) were studied in PCP-treated animals. L-NAME potentiated PC P-induced behaviours and c-fos expression in many brain regions. The greate st increases were observed in the frontal, retrosplenial granular cortex, c erebellum, thalamic and subthalamic nuclei. While PCP alone induced low c-S os expression in the entorhinal cortex, with almost no expression in the ro stral part of caudate putamen, animals pretreated with L-NAME showed marked activation in these brain areas. These results strongly indicate the invol vement of the nitric oxide system in the mechanism of action of PCP. (C) 20 00 Elsevier Science B.V. All rights reserved.