Interactions of phencyclidine with hippocampal circuitry: evidence for neuronal heterogeneity.

The discovery of phencyclidine (PCP) receptors has stimulated the search for specific PCP antagonists. A direct product of this research is metaphit, an irreversible PCP ligand, which has recently been synthesized. In this study we examined the effects of metaphit on the responses of hippocampal neurons to PCP. On the basis of unfiltered action potential durations, hippocampal cells were divided into two groups, complex-spike cells and theta neurons. Local application of PCP caused inhibitions of the spontaneous firing rates of complex-spike cells. Metaphit, locally applied, antagonized approximately 50% of these responses, while the remaining responses were unaffected. In contrast, PCP caused increases in the spontaneous firing rates of theta cells and in almost all cases, these responses to PCP were attenuated by metaphit administration. These effects of metaphit were specific for PCP as the responses to locally applied norepinephrine were not altered by metaphit. The data suggest two mechanisms of action of PCP in the hippocampus. In addition, these mechanisms may be localized in part to different cell types.