Effects of phencyclidine on the release of radioactivity from rat striatal slices labeled with [³H]choline

Phencyclidine (PCP) has been shown to antagonize the effects of acetylcholine (ACh) in a variety of systems and to inhibit the binding of muscarinic antagonists to brain membranes. Therefore, we have studied the effects of PCP on ACh release from rat striatal slices in order to characterize the effect of PCP in a central cholinergic system. After incubation with [³H]choline, striatal slices were superfused and the superfusate was assayed for radioactivity. The presence of PCP led to dose-related inhibition of K⁺-stimulated ACh release. This may be due to the reported ability of PCP to enhance dopamine release as both direct (pergolide) and indirect (amphetamine) dopamine agonists also inhibited striatal ACh release. Haloperidol blocked the inhibitory effects of PCP, amphetamine and pergolide on ACh release, supporting the notion that the decrease in ACh release produced by PCP is mediated indirectly via the release of dopamine onto cholinergic neurons.