Neuroleptic-induced changes in the firing pattern of guinea pig nigrostriatal neurons

Abstract

It is well established that neuroleptics increase the firing rate of nigrostriatal neurons. However, the action of these drugs on firing pattern has received scant attention. The effect of local administration of neuroleptic agents was investigated on the firing pattern, and also firing rate, of nigrostriatal neurons. Chlorpromazine or haloperidol was microinjected into the substantia nigra of the urethane-anaesthetized guinea pig during extracellular recordings from identified nigrostriatal cells. Both neuroleptics induced the familiar increase in firing rate of nigrostriatal neurons. More significantly, however, these drugs also caused a dose-dependent change in firing pattern, specific to neuroleptic action. This change consisted of a drug-induced transition from slow irregular single or double spikes with a short interspike interval ('beat' firing) to irregular bursts of spikes with a longer interspike interval ('burst' firing). Furthermore, the transition from beat to burst firing occurred sharply and sometimes continued to switch in a regular cyclical fashion between the two modes for up to three hours following infusion of the neuroleptic. Administration of neuroleptics may thus provide a useful tool for studying the physiology of the firing pattern of nigrostriatal neurons.