Differential interactions of phencyclidine with tetrabenazine and reserpine affecting intraneuronal dopamine

This study has examined the effects on synaptosomal (P2) dopamine of interactions of phencyclidine and some other stimulants with tetrabenazine and reserpine. Tetrabenazine and reserpine both enhanced the spontaneous synaptosomal release of [14C]dopamine and inhibited its formation from [14C]phenylalanine. The [14C]dopamine formation increases induced by phencyclidine and amfonelic acid, however, were affected differentially by coadditions of tetrabenazine and reserpine. At the lower concentrations, tetrabenazine either did not affect or augmented the dopamine formation enhancements by the stimulants. Reserpine at all levels blocked the synthesis enhancements and revealed inhibitory effects of phencyclidine and amfonelic acid upon dopamine formation; only at the highest concentration did the action of tetrabenazine mimick that of reserpine. Amphetamine stimulation of dopamine formation was affected by tetrabenazine and reserpine alike; the stimulation was either maintained or enhanced. Ketamine did not affect dopamine formation either by itself, with tetrabenazine, or with reserpine. In summary, tetrabenazine and reserpine affected synaptosomal dopamine formation and release in a comparable manner, but intraneuronal dopaminergic actions of phencyclidine and also of amfonelic acid may be influenced differentially by these two releasing agents.