1 Phencyclidine (PCP) is widely used as an animal model of schizophrenia. The aim of this study was to better understand the role of nitric oxide (NO) in the mechanism of action of PCP and to determine whether positive NO modulators may provide a new approach to the treatment of schizophrenia. 2 The eects of the NO donor, sodium nitroprusside (SNP), were studied in PCP-treated rats. Following drug administration, behavioural changes and the expression of c-fos, a metabolic marker of functional pathways in the brain, were simultaneously monitored. 3 Acute PCP (5 mg kg 71 , i.p.) treatment induced a complex behavioural syndrome, consisting of hyperlocomotion, stereotyped behaviours and ataxia. Treatment with SNP (2 ± 6 mg kg 71 , i.p.) by itself produced no eect on any behaviour studied but completely abolished PCP-induced behaviour in a dose-and time-dependent manner. 4 PCP had dierential regional eects on c-fos expression in rat brain, suggesting regionally dierent patterns of neuronal activity. The most prominent immunostaining was observed in the cortical regions. Pre-treatment with SNP blocked PCP-induced c-fos expression at doses similar to those that suppress PCP-induced behavioural eects. 5 These results implicate the NO system in the mechanism of action of PCP. The fact that SNP abolished eects of PCP suggests that drugs targeting the glutamate-NO system may represent a novel approach to the treatment of PCP-induced psychosis and schizophrenia.

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Six male Sprague-Dawley rats were trained on a DRL-20 operant schedule for food presentation. When stable performance was established, they were exposed to an escalating regimen of daily ethanol administration (1.125-3.75 g/kg, IP). This dosing regimen continued until the maximally tolerable dose for each subject was reached. Tolerance loss then was monitored for approximately 6 months by periodic ethanol challenge doses (1.5 g/kg). Dose-effect curves (DECs) were obtained prior to (DEC-1), immediately after (DEC-2), and 6 months following termination of (DEC-3) the ethanol exposure. Rate-increasing effects (DEC-1) were noted at low doses (0.75 and 1.125 g/kg), with a higher dose (2.25 g/kg) resulting in a decreased rate of responding. Tolerance, following chronic ethanol exposure, developed to both the rate-increasing and rate-decreasing effects of ethanol (DEC-2). While some tolerance was lost within the 6 months following the daily ethanol exposure (DEC-3), a significant degree of tolerance was still indicated by most of the response measures. This duration of tolerance was considerably longer than that generally reported, and is probably attributable to persistent learned compensatory behavior and/or intermittent ethanol challenge tests.