Chronic clozapine versus chronic haloperidol treatment: differential effects on electrically evoked dopamine efflux in the rat caudate putamen, but not in the nucleus accumbens.

Abstract

Fast cyclic voltammetry at carbon-fibre micro-electrodes was used to investigate the effects of chronic clozapine or haloperidol administration on electrically evoked dopamine efflux in the nucleus accumbens and caudate putamen of the anaesthetized rat. Stimulation trains were delivered to the median forebrain bundle (60 pulses, 350 microns duration) every 5 min, and the evoked dopamine efflux measured as a function of a) the applied stimulus intensity (range 0.2 mA-1.0 mA), and b) the applied stimulus frequency (range 10 Hz-250 Hz). Chronic administration of either clozapine (20 mg/kg x 21 days, p.o.) or haloperidol (1 mg/kg x 21 days, p.o.) significantly reduced electrically evoked dopamine efflux in the nucleus accumbens over the range of stimulus intensities and frequencies tested. The reduction in evoked dopamine efflux observed in the nucleus accumbens of clozapine- and haloperidol-treated rats showed no statistically significant difference. In contrast, only chronic haloperidol treatment significantly reduced evoked dopamine efflux in the caudate putamen. These findings demonstrate that chronic treatment with either the atypical neuroleptic, clozapine, or the typical neuroleptic, haloperidol, produce long-term changes in mesolimbic dopamine function; actions which may underlie their antipsychotic efficacy. They also provide further evidence that the sparing action of clozapine on nigrostriatal dopamine activity may underlie the lower incidence of extrapyramidal side effects associated with its long-term administration.