Disturbances in the balance of regional brain dopaminergic activity have been implicated in the symptomatology of schizophrenia. Recent studies suggest that dysfunction of the dorsolateral prefrontal cortex (DLPFC) may cause the impaired motivation, shallow affect, and deficiencies in the performance of problem solving tasks suffered by schizophrenics. Similar deficits are produced in primates by dopamine depletion in the DLPFC. Together these observations suggest a role for DLPFC dopaminergic neurons in cognitive functions subserved by this area. In one series of experiments in rats, dopamine depletion in the medial frontal cortex (MFC), a possible rodent homologue of the DLPFC of primates, resulted in increased dopaminergic activity in striatum. Our observations in rats showed that dopamine depletion in the MFC by local injection of MPP+ or 6- OHDA was associated with increased dopaminergic in nucleus accumbens, but not the caudatoputamen. This project will now be extended to primates to further test the hypothesis that corticostriatal abnormalities underlie psychotic disorders in a species more closely related and similar to humans.
