MPTP LESIONS OF THE NIGROSTRIATAL DOPAMINERGIC PROJECTION DECREASE [H-3] 1-[1-(2-THIENYL)CYCLOHEXYL]-PIPERIDINE BINDING TO PCP SITE-2 - FURTHER EVIDENCE THAT PCP SITE-2 IS ASSOCIATED WITH THE BIOGENIC-AMINE REUPTAKE COMPLEX

Our previous studies have demonstrated that, using membranes of guinea pig brain, [H-3]1-[1-(2-thienyl)cyclohexyl]piperidine ([H-3]TCP) labels not only the phencyclidine binding site associated with the NMDA receptor (PCP site 1), but also a second high affinity binding site which is associated with the biogenic amine reuptake carrier (termed PCP site 2). To test this hypothesis, the binding of [H-3]GBR12935 to the dopamine transporter, and [H-3]TCP binding to PCP sites 1 and 2 were measured in caudates harvested from control, MPTP-treated and reserpine-treated dogs. MPTP treatment decreased dopamine levels by over 99%, decreased [H-3]GBR12935 binding by over 90%, decreased [H-3]TCP binding to PCP site 2 by about 50%, and had no significant effect on [H-3]TCP binding to PCP site 1. These data are consistent with the hypothesis that a portion of PCP site 2 is associated with dopaminergic nerve terminals in dog caudate.