CHRONIC CLOZAPINE VERSUS CHRONIC HALOPERIDOL TREATMENT - DIFFERENTIAL-EFFECTS ON ELECTRICALLY-EVOKED DOPAMINE EFFLUX IN THE RAT CAUDATE-PUTAMEN, BUT NOT IN THE NUCLEUS-ACCUMBENS

Fast cyclic voltammetry at carbon-fibre microelectrodes was used to in vestigate the effects of chronic clozapine or haloperidol administrati on on electrically evoked dopamine efflux in the nucleus accumbens and caudate putamen of the anaesthetized rat. Stimulation trains were del ivered to the median forebrain bundle (60 pulses, 350 mu s duration) e very 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 app lied stimulus frequency (range 10 Hz-250 Hz). Chronic administration o f 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 ef flux in the nucleus accumbens over the range of stimulus intensities a nd frequencies tested. The reduction in evoked dopamine efflux observe d in the nucleus accumbens of clozapine- and haloperidol-treated rats showed no statistically significant difference. In contrast, only chro nic haloperidol treatment significantly reduced evoked dopamine efflux in the caudate putamen. These findings demonstrate that chronic treat ment with either the atypical neuroleptic, clozapine, or the typical n euroleptic, haloperidol, produce long-term changes in mesolimbic dopam ine function; actions which may underlie their antipsychotic efficacy. They also provide further evidence that the sparing action of clozapi ne on nigrostriatal dopamine activity may underlie the lower incidence of extrapyramidal side effects associated with its long-term administ ration.