Abstract
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 (TR(ACh) in various areas of the rat brain. In doses of 14.3 to 114.4 μmol/kg (i.p.), phencyclidine increased the (TR(ACh) 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 (TR(ACh) in the hippocampus or striatum. The increases in cortical and diencephalic (TR(ACh) were temporally correlated with the behavioral activity elicited by phencyclidine. A 7 day chronic treatment regimen (28.6 μmol/kg/day) provided no evidence for tolerance development to the effects of phencyclidine on the (TR(ACh) 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.