Chronic haloperidol treatment enhances binding to NMDA receptors in rat cortex

Hyperactivity of the dopaminergic system and a hypoglutamatergic state have been hypothesized to underlie schizophrenia. It has also been proposed that neuroleptics may interact not only with the dopaminergic system but also with the glutamatergic system. We found that daily intraperitoneal injections of haloperidol (1 mg kg-1) for 21 days resulted in increased binding (10-20%) to the NMDA type of glutamate receptors in the outer layers of rat parietal cortex. Quantitative receptor autoradiography indicates that the action of haloperidol is regionally specific since no changes in NMDA receptors were found in the hippocampus and thalamus. Our data suggest that haloperidol may exert its antipsychotic effects by enhancement of glutamatergic functions as well as by the blockade of dopamine receptors.