Inhibition by phencyclidine of excitatory amino acid-stimulated release of neurotransmitter in the nucleus accumbens.

The effects of phencyclidine (PCP) on the release of acetylcholine and dopamine, stimulated by excitatory amino acid agonists was examined in slices of nucleus accumbens of the rat. In slices incubated in [3H]choline or [3H]dopamine, the amount of tritium efflux produced by 1 mM N-methyl-D-aspartate (NMDA), kainic acid (KA) or quisqualic acid (QA) was compared with that produced in the presence of varying concentrations of phencyclidine. N-Methyl-D-aspartate stimulated the calcium-dependent release of both ACh and DA, which was completely inhibited by physiological concentrations of magnesium and inhibited by 2-aminophosphonovalerate (2-APV). Kainic acid- and quisqualic acid-stimulated release of ACh and DA was partially inhibited by magnesium or by 2-APV. Phencyclidine inhibited NMDA-stimulated release of ACh and DA with IC50's around 100 nM. Phencyclidine (0.1 microM) also significantly inhibited kainic acid and quisqualic acid-induced release of ACh in magnesium-free but not magnesium-containing buffer, suggesting that the effect of PCP on kainic acid- and possibly quisqualic acid-stimulated release of ACh is on that part of the response which is mediated by NMDA receptors. The results suggest that the inhibition by PCP of the release of ACh and DA in the nucleus accumbens is selective for NMDA-type receptors.