Phencyclidine: behavioral and biochemical evidence supporting a role for dopamine

Pharmacological studies of phencyclidine (PCP)-induced behaviors such as stereotypy and turning suggest that PCP is an indirectly acting dopamine (DA) agonist with some anticholinergic potential. In vitro studies show that PCP is a potent, competitive inhibitor of monoamine uptake. PCP has also been shown to stimulate synaptosomal striatal tyrosine hydroxylase activity via a release of DA (which normally inhibits this enzyme). The mechanism by which PCP releases DA is unknown, but is similar to that of methylphenidate and distinct from that of amphetamine. In vivo studies also show similarities between PCP and the nonamphetamine class of stimulants. For example, PCP and amfonelic acid, but not amphetamine, potentiate haloperidol-induced DA metabolism. This effect can be blocked by baclofen, which suggests a dependence on nigrostriatal impulse flow. Other studies suggest that PCP releases a pool of DA that is in rapid equilibrium with the vesicular compartment, thereby activating a feedback mechanism (probably transsynaptic) that inhibits the synthesis of DA. Despite the similarities between PCP and nonamphetamine stimulants, there are both behavioral and biochemical anomalies that caution against the strict classification of PCP as a nonamphetamine stimulant.