Subchronic Effects of Phencyclidine on Dopamine and Serotonin Receptors: Implications for Schizophrenia

Changes in representative dopamine (D-1, D-2, and D-4) and serotonin (5-HT1A and 5-HT2A) receptors that have been implicated in the pathophysiology and treatment of schizophrenia were autoradiographically quantified after subchronic phencyclidine (PCP) treatment (2 mg/kg for 7 days, bi-daily followed by 7 days drug free). This treatment has consistently induced robust and long-lasting cognitive deficits in adult rats, although the molecular mechanisms contributing to PCP-induced cognitive deficits remain undefined. Repeated PCP treatment significantly decreased labeling of D-1 receptors in the medial and lateral caudate-putamen (22% and 23%, respectively) and increased 5HT(1A) receptor binding in the medial-prefrontal (26%) and dorsolateral-frontal cortex (30%). No changes in D-1 or 5HT(1A) receptors were detected in other brain regions. These findings suggest that downregulation of striatal D-1 receptors and upregulation of cortical 5HT(1A) receptors may contribute to PCP-induced impairment of cognitive functions in rats. Subchronic PCP treatment did not alter levels of D-2, D-4, and 5HT(2A) receptors in all brain regions examined, which suggests a minimal role for these receptors in mediating subchronic actions of PCP in adult rats.