Chronic haloperidol and clozapine administration increases the number of cortical NMDA receptors in rats

The aim of the present study was to examine the influence of 3-month admini stration of haloperidol (1 mg/kg per day) and clozapine (50 mg/kg per day) in drinking water on cortical NMDA (N-methyl-D-aspartate) receptors in rats . On day 5 of withdrawal, the animals were killed and their brains were rem oved. The binding of [H-3]MK-801 ([H-3](5R,10S)-(+)5-methyl-10,11-dihydro-5 H-dibenzo[a,d]cyclohepten-5, 10-imine) and [H-3]CGP 39653([H-3]D,L-(E)-2-am ino-4-propyl-5-phosphono-3-pentenoic acid) to NMDA receptors in different c ortical areas, as well as the binding of [H-3]spiperone to dopamine D-2 rec eptors in the striatum, were analysed by quantitative autoradiography. Halo peridol increased the binding of [H-3]CGP 39653 in frontal, insular and par ietal cortices. Clozapine increased the binding of [H-3]CGP 39653 in insula r and parietal cortices. Haloperidol, bur not clozapine, increased the bind ing of [H-3]spiperone in the striatum. None of the neuroleptics influenced the binding of [H-3]MK-801 to cortical NMDA receptors. An additional assay revealed an increase in the B-max value, with no significant changes in the K-D of [H-3]CGP 39653 binding in parieto-insular cortical homo-genates as a result of haloperidol and clozapine administration. The present results suggest that long-term treatments with haloperidol and clozapine increase the number of NMDA receptors in different cortical regio ns.