Analysis of sociability and preference for social novelty in the acute and subchronic phencyclidine rat.

Both acute and sub-chronic phencyclidine administration produce behavioural and pathophysiological changes that resemble some features of schizophrenia. The present study aimed to determine if acute and sub-chronic phencyclidine treatment in male rats produces deficits in sociability and social novelty preference, which may reflect aspects of the negative symptomatology observed in schizophrenia. Rats were treated with phencyclidine acutely (2 or 5 mg/kg) or subchronically (2 or 5 mg/kg bi-daily for one week followed by a one week wash-out period) or vehicle. Social affiliative behaviour was assessed using the sociability and preference for social novelty paradigm where social interaction time was measured in (a) a chamber containing an unfamiliar conspecific vs an empty chamber (sociability), or (b) a chamber containing an unfamiliar conspecific vs a chamber containing a familiar conspecific (preference for social novelty). Results showed that acute administration of phencyclidine produced a reduction in measures of sociability but had no effect on preference for social novelty while sub-chronic administration of phencyclidine had no effect on sociability or social novelty. This study provides further evidence for the usefulness of phencyclidine models in modelling the symptomatology of schizophrenia.

Effect of pretreatment with risperidone on phencyclidine-induced disruptions in object recognition memory and prefrontal cortex parvalbumin immunoreactivity in the rat.

Sub-chronic administration of phencyclidine to the rat induces enduring cognitive and pathophysiological changes that resemble some features of schizophrenia. The present study aimed to determine if concurrent administration of the atypical antipsychotic, risperidone, could attenuate the effect of phencyclidine on object recognition memory and parvalbumin-containing neurons in the prefrontal cortex. Rats were administered phencyclidine at a dose of 2mg/kg i.p. bi-daily for 1 week, or vehicle. Half of the phencyclidine group was concurrently treated with risperidone (0.5mg/kg i.p.) twice daily for 10 days, beginning 3 days before the start of phencyclidine administration. Novel object recognition memory and subsequent brain analysis were assessed 6 weeks post-phencyclidine treatment. Phencyclidine produced a deficit in object recognition memory as measured by the discrimination ratio. In addition, 6 weeks post-phencyclidine, analysis of brains showed a reduction in expression of parvalbumin-immunoreactive neurons in the prefrontal cortex, with specific deficits observed in the prelimbic region, but not infralimbic or cingulate cortices. Concurrent administration of risperidone showed no protective effects against these deficits. These results show the importance of the sub-chronic phencyclidine rat in modelling cognitive and prefrontal pathophysiology observed in schizophrenia, but suggest that concurrent risperidone is not neuroprotective in this model.

Disturbances in social interaction occur along with pathophysiological deficits following sub-chronic phencyclidine administration in the rat.

A sub-chronic administration of phencyclidine to the rat brings about enduring pathophysiological and cognitive changes that resemble some features of schizophrenia. The present study aimed to determine whether the behavioural consequence of this phencyclidine regime extends to a long-term disruption of social interaction that might provide a parallel with some negative symptoms of the disease. Rats were treated with phencyclidine (2mg/kg bi-daily for 1 week) or vehicle followed by a drug-free period. Social interaction was assessed 24h, 1 week, 3 weeks and 6 weeks post-treatment. A long-lasting disturbance of social behaviour was observed in the phencyclidine group, namely more contact and non-contact interaction with an unfamiliar target rat at all time points. Six weeks post-phencyclidine, analysis of brains showed a reduction in expression of parvalbumin immunoreactive neurons in the hippocampus with significant reductions localised to the CA1 and dentate gyrus regions. These results show that sub-chronic phencyclidine produces long-lasting disruptions in social interaction that, however, do not model the social withdrawal seen in patients with schizophrenia. These disturbances of social behaviour may be associated with concurrent pathophysiological brain changes.