PREFERENTIAL ACTIVATION OF CORTICAL DOPAMINE NEUROTRANSMISSION BY CLOZAPINE - FUNCTIONAL-SIGNIFICANCE

Dopamine projections to the prefrontal cortex are thought to be essent ial for the proper functioning of this region and are proposed to be i nvolved in negative (deficit) symptomatology of schizophrenia. Our stu dies in the rodent indicate that clozapine, the most effective antipsy chotic drug for the treatment of negative symptoms, causes an increase in the basal output of dopamine neurons projecting to the prefrontal cortex. This finding is in contrast to the effect of clozapine in the basal ganglia and the effect of typical antipsychotic drugs such as ha loperidol in the prefrontal cortex. The ability of clozapine to increa se dopamine release in the prefrontal cortex and its relatively weak a ffinity for some types of dopamine receptors suggest that this drug ma y exert its therapeutic influence in part by increasing dopaminergic f unction in the prefrontal cortex.