A COMMON ACTION OF CLOZAPINE, HALOPERIDOL, AND REMOXIPRIDE ON D-1-DOPAMINERGIC AND D-2-DOPAMINERGIC RECEPTORS IN THE PRIMATE CEREBRAL-CORTEX

The potencies of the major neuroleptics used in the treatment of schizophrenia, including haloperidol and remoxipride, correlate with their ability to bind D-2-dopaminergic receptors in subcortical structures. On the other hand, the neuroleptic clozapine has a low affinity for these sites, and the pharmacological basis of its beneficial action is less clear. We have found that chronic treatment with clozapine, haloperidol, and remoxipride up-regulates D-2 receptors in specific cortical areas of the rhesus monkey frontal, parietal, temporal, and occipital lobes. Of particular interest, all three neuroleptics down-regulated D-1 receptors in prefrontal and temporal association regions-the two areas most often associated with schizophrenia. This latter finding raises the possibility that down-regulation of D-1 receptors in prefrontal and temporal cortex may be an important component of the therapeutic response to neuroleptic drugs. Further, the common effects of three neuroleptics with different pharmacological profiles in the cerebral cortex is consistent with the idea that this structure is a major therapeutic target in the treatment of schizophrenia.