The effect of phencyclidine on the turnover rate of acetylcholine in various regions of rat brain.

Although the mechanism of action of phencyclidine is poorly understood, an interaction of phencyclidine with central cholinergic systems has been proposed. To test this hypothesis directly, we investigated the effects of this compound on the turnover rate of acetylcholine (TRACh) in various areas of the rat brain. In doses of 14.3 to 114.4 mumol/kg (i.p.), phencyclidine increased the TRACh in the frontal cortex, parietal cortex and diencephalon when rats were sacrificed 30 min after drug treatment. In contrast, these doses of phencyclidine had no effect on the TRACh in the hippocampus or striatum. The increases in cortical and diencephalic TRACh were temporally correlated with the behavioral activity elicited by phencyclidine. A 7 day chronic treatment regimen (28.6 mumol/kd/day) provided no further evidence for tolerance development to the effects of phencyclidine on the TRACh in the frontal cortex or diencephalon. These results demonstrate that phencyclidine differentially affects cholinergic dynamics in various areas of the rat brain. The neurochemical profile of phencyclidine reported herein is similar to those previously described for central stimulants such as d-amphetamine, nomifensine and cocaine.