PHENCYCLIDINE AND THE MIDBRAIN DOPAMINE SYSTEM - ELECTROPHYSIOLOGY AND BEHAVIOR

Phencyclidine (PCP) and PCP-like drugs increased firing rates and the amount of burst activity of A10 dopamine neurons recorded extracellula rly in anesthetized rats. These effects correlated to their potency as noncompetitive N-methyl-D-aspartate (NMDA) antagonists but not to the ir affinity for the u- receptor. In contrast, the direct acting NMDA a ntagonists, CGS 19755, (+)CPP and NPC 12626, produced no alterations i n either firing rate or burst patterns. However, pretreatment with eit her CGS 19755 or (+)CPP effectively attenuated the excitatory effects of PCP. In contrast to the findings obtained in the whole animal, PCP in the midbrain slice preparation did not activate dopamine neurons, e ven though PCP selectively blocked the excitations induced by NMDA but not those of the nonNMDA agonists, kainate and AMPA. In the self-admi nistration test system a progressive-ratio schedule of reinforcement w as used to assess the reinforcing strength of PCP and the PCP congener s, TCP and BTCP. In comparison to BTCP, which produced breaking points comparable to those occurring with equivalent doses of cocaine, PCP a nd TCP had considerably less reinforcing efficacy. These behavioral di fferences appeared to reflect the affinity of the compounds for the do pamine reuptake site versus the PCP binding site on the NMDA-ion chann el complex. Thus, PCP's psychotomimetic effects and abuse liability pr operties may result from the differential mechanisms by which it affec ts limbic and cortical dopamine neurotransmission.