Subchronic effects of phencyclidine on dopamine and serotonin receptors: Implications for schizophrenia

Changes in representative dopamine (D1, D2, and D4) 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) trea ment (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 decrea ed labeling of D1 receptors in the medial and lateral caudate-putamen (22% and 23%, respectively) and increased 5HT1A receptor binding in the medial-prefrontal (26%) and dorsolateral-frontal cortex (30%). No changes in D1 or 5HT1A receptors were detected in other brain regions. These findings suggest that downregulation of striatal D1 receptors and upregulation of cortical 5HT1A receptors may contribute to PCP-induced impairment of cognitive functions in rats. Subchronic PCP treatment did not alter levels of D2, D4, and 5HT2A receptors in all brain regions examined, which suggests a minimal role for these receptors in mediating subchronic ac ions of PCP in adult rats. Copyright © Humana Press 2009.