Phencyclidine (PCP) mimics many aspects of schizophrenia, yet the underlying mechanism of neurochemical adaptation for PCP is unknown. We therefore used proteomics to study changes in the medial prefrontal cortex in animals with PCP-induced behavioural deficits. Male Wistar rats were injected with saline or 5？mg/kg phencyclidine for 5 days followed by two days of washout. Spontaneous alternation behaviour was tested in a Y-maze and then proteins were extracted from the medial prefrontal cortex. 2D-DIGE analysis followed by spot picking and protein identification with mass spectrometry then provided a list of differentially expressed proteins. Treatment with 5？mg/kg phencyclidine decreased the percentage of correct alternations in the Y-maze compared to saline-treated controls. Proteomics analysis of the medial prefrontal cortex found upregulation of 6 proteins (synapsin-1, Dpysl3, Aco2, Fscn1, Tuba1c, and Mapk1) and downregulation of 11 (Bin1, Dpysl2, Sugt1, ApoE, Psme1, ERp29, Pgam1, Uchl1, Ndufv2, Pcmt1, and Vdac1). A trend to upregulation was observed for Gnb4 and Capza2, while downregulation trends were noted for alpha-enolase and Fh. Many of the hits in this study concur with recent postmortem data from schizophrenic patients and this further validates the use of phencyclidine in preclinical translational research. 1. Introduction Schizophrenia is a complex, relapsing psychiatric disorder featuring both positive and negative symptoms. Developing medication to treat schizophrenia has been difficult, and various animal models have been proposed to aid the search for treatments. For example, the MATRICS battery of tests is now used to screen the efficacy of novel compounds [1] and groups such as Bussey and colleagues are continually optimizing these methods for use on a larger scale or by industry [2]. One can mimic the symptoms of schizophrenia clinically with the unselective compound phencyclidine (PCP) [3]. Repeated injection of PCP in animals induces dysfunction of the prefrontal cortex which can be measured both behaviourally and neurochemically [4]. However, comparison of these results is complicated by the multitude of injection schedules and protocols depending on animal (e.g., rat versus mouse) or strain in question [5–10]. Given the diversity of phencyclidine protocols, it is important to validate our results with others and with the clinical situation. The underlying neurochemical changes induced by PCP in the medial prefrontal cortex are still not well understood. Most methods have focused on metabolic measures (e.g., glucose utilization)
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