Phencyclidine binding sites in the nucleus accumbens and phencyclidine-induced hyperactivity are decreased following lesions of the mesolimbic dopamine system

[³H]Phencyclidine ([³H]PCP) binding to rat nucleus accumbens, hippocampal and striatal membranes, and PCP-induced locomotor hyperactivity were assessed following selective lesions of the mesolimbic dopaminergic system. 6-Hydroxydopamine (6-OHDA) injections into the A₁₀ region of the ventral tegmental area or into the accumbens itself resulted in a blockade of PCP's stimulatory effects and a highly significant reduction in the number of [³H]PCP binding sites and dopamine content of the nucleus accumbens. However, destruction of the dopaminergic mesolimbic fibers did not significantly alter hippocampal or striatal [³H]PCP binding. The data suggest that PCP elicits its locomotor stimulating effects via an interaction with PCP binding sites located mostly on mesolimbic dopaminergic terminals within the nucleus accumbens.