Subchronic Phencyclidine Treatment Decreases the Number of Dendritic Spine Synapses in the Rat Prefrontal Cortex

Background A growing body of evidence suggests the existence of synaptic pathology in schizophrenia. Here we used the phencyclidine schizophrenia model to directly investigate at the electron microscopic level whether structural synaptic alterations are present in these animals. Methods Adult male rats were treated according to our subchronic phencyclidine paradigm (5 mg/kg twice daily for 7 days, intraperitoneally). Following a one-week withdrawal period, the number of prefrontal cortical spine synapses was calculated using an unbiased electron microscopic stereological approach. The number of astroglia cells and the density of their processes was also analyzed following glial-fibrillary acidic protein immunohistochemistry. Results Subchronic phencyclidine treatment resulted in a 41.2% decrease in the number of prefrontal spine synapses when compared to controls. This was accompanied by a 58.8% increase in astroglia process density, without significant change in the number of astroglia cells. Conclusions Our results demonstrate a severe reduction in the number of prefrontal spine synapses in an animal model of schizophrenia. This phenomenon may contribute to phencyclidine-induced cognitive dysfunction and decreased prefrontal cellular activity observed in this model. A growing body of evidence suggests the existence of synaptic pathology in schizophrenia. Here we used the phencyclidine schizophrenia model to directly investigate at the electron microscopic level whether structural synaptic alterations are present in these animals. Adult male rats were treated according to our subchronic phencyclidine paradigm (5 mg/kg twice daily for 7 days, intraperitoneally). Following a one-week withdrawal period, the number of prefrontal cortical spine synapses was calculated using an unbiased electron microscopic stereological approach. The number of astroglia cells and the density of their processes was also analyzed following glial-fibrillary acidic protein immunohistochemistry. Subchronic phencyclidine treatment resulted in a 41.2% decrease in the number of prefrontal spine synapses when compared to controls. This was accompanied by a 58.8% increase in astroglia process density, without significant change in the number of astroglia cells. Our results demonstrate a severe reduction in the number of prefrontal spine synapses in an animal model of schizophrenia. This phenomenon may contribute to phencyclidine-induced cognitive dysfunction and decreased prefrontal cellular activity observed in this model.