Phenylclindine-induced alteration in rat muscarinic cholinergic receptor regulation

A muscarinic cholinergic receptor binding profile was performed on 3 separate regions of the rat brain following administration of the drug phencyclidine (10 mg/kg, twice a day) for 10 days. Binding assays were performed on homogenates of the hippocampus, striatum and cortex using the ligand [3H]QNB. Scatchard analysis of the binding data revealed a statistically significant decrease in the number of [3H]QNB binding sites in all phencyclidine treated animals. Binding was 22% lower in the cortex and 16% lower in the hippocampus and striatum. Phencyclidine treatment did not significantly alter the affinity of the receptor for the ligands [3H]QNB, acetylcholine or phencyclidine. This decrease in CNS muscarinic receptors could be contributing to the underlying biochemical mechanism of tolerance to the drug.