Electrophysiological effects of phencyclidine on rat hippocampal pyramidal neurons

Abstract

The effects of local application of phencyclidine to hippocampal CAl pyramidal neurons was investigated using electrophysiological techniques. The predominant response was a decrease in firing rate, although excitation and biphasic responses were also seen. The stereospecificity of these responses was demonstrated using the (+) and (−) isomers of 1-[1-phenylcyclohexy]-3-methylpiperidine (PCMP). The (+) enantiomer was 4–15 times more potent than the (−) enantiomer. Interactions between PCP and catecholaminergic synapses were also investigated. Catecholamine depletion by reserpine markedly increased the amount of phencyclidine needed to elicit effects on cell discharge; in many cases, no response was seen with the largest dose of phencyclidine tested. The α-adrenergic antagonist, phentolamine, reversibly antagonized phencyclidine-induced inhibition in the firing rate of CAl cells but did not seem to affect excitation; in contrast, timolol, a β-adrenergic antagonist, did not affect the depression but seemed to antagonize reversibly the phencyclidine-induced excitations. It is concluded that the mechanism of phencyclidine-induced changes in pyramidal neuron discharge involves adrenergic input to these cells.