Effects of chronic phencyclidine on fixed-ratio responding: no relation to neurotransmitter receptor binding in rat cerebral cortex.

The effects of chronic phencyclidine (3.2 mg/kg for 25 days) on responding maintained under a fixed-ratio 30 schedule of food presentation were studied in rats. Initially phencyclidine produced large decreases in the overall rate of responding. This decrease was due primarily to long pauses in responding and secondarily to a decrease in local rates of responding. Although tolerance developed to the rate-decreasing effects of phencyclidine in each subject, the extent and pattern of its development differed among the subjects. After the chronic drug regimen, the rats were sacrificed. Ligand binding to muscarinic cholinergic, opiate, adrenergic, and serotonergic receptors in cortex was then compared to that in rats which received saline with operant training, phencyclidine alone, or saline alone. Neither operant behavior alone, phencyclidine alone, nor the interaction of phencyclidine and operant behavior was found to alter binding to these receptors. These results indicate that behavioral tolerance develops to phencyclidine, but it is not accompanied by changes in binding to the receptors studied.