The electrophysiological characterization of phencyclidine analogs on ventral tegmental area dopamine neurons

Abstract

This study was designed to characterize the effects of PCP and PCP derivatives on dopamine systems using electrophysiological and behavioral methods. TCP, a high affinity PCP/NMDA receptor ligand only increased A10 firing while BTCP, a high affinity DA reuptake ligand only decreased activity. PCP with similar affinity for the NMDA and reuptake sites, produced a dose dependent bimodal change in the activity of A10 neurons. Lesions of the nucleus accumbens or treatment with picrotoxin, a GABA antagonist attenuated the BTCP and high dose PCP inhibitory effects thus supporting the existence of a GABAergic accumbal-VTA feedback pathway. Furthermore, BTCP and PCP produced significant increases in locomotor activity which were attenuated by accumbens lesions. The present data provide an explanation for PCP's bimodal effects and possibly for its psychotomimetic properties as well as abuse liability which may reside with its blockade of dopamine reuptake in the mesolimbic system.