Investigation into the use of phencyclidine in modelling the symptoms of schizophrenia - neurochemical and behavioural studies in the rat

• Main Author: McKibben, Claire
• Published: Queen's University Belfast 2015
• Subjects: 616.89
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.680433

Schizophrenia is a chronic, severely debilitating psychiatric disorder that affects up to 1 % of the population worldwide. The N-methyl-D-aspartic acid (NMDA) receptor antagonist phencyclidine (PCP) can produce a syndrome in normal healthy humans that closely resembles the positive, negative and cognitive symptoms seen in schizophrenia and can exacerbate symptoms in patients with chronic schizophrenia. Furthermore, administration of PCP in animals results in behavioural, metabolic, neuropathological and electrophysiological changes modelling various aspects of schizophrenia symptomatology. The aim of these studies was to investigate the ability of a sub-chronic PCP treatment regime in adult rats to produce long lasting behavioural and neurochemical alterations with particular relevance to those observed in schizophrenia. Long term effects on behavioural, cognitive, and neuropathological endpoints were determined in adult Lister Hooded rats following sub-chronic PCP administration (7-days bi-daily dosing at 2mg/kg). Sub-chronic PCP treatment resulted in deficits in recognition memory using the novel object recognition (NOR) test, which reflects aspects of the cognitive symptomatology observed in schizophrenia. We observed deficits in social interaction using our existing methodology in the social interaction paradigm and also using a novel paradigm, the sociability and social novelty preference test, effectively mirroring some of the negative symptoms of schizophrenia. Behavioural sensitisation was firmly established following sub-chronic PCP treatment and co-administration with the antipsychotic risperidone was shown to attenuate the PCP-induced locomotor effect. Enhancement of locomotor activity is considered to be equivalent to certain aspects of the positive symptoms of schizophrenia. Deficits in parvalbumin immunoreactivity (PV-IR) were detected in the prefrontal cortex (PFC) but not in the hippocampus following sub-chronic PCP treatment. In conclusion, the results from these studies are supportive of sub-chronic PCP administration being a valid animal model for assessing a variety of the behavioural and neuropathological deficits associated with schizophrenia.