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 administration of haloperidol (1 mg/kg per day) and clozapine (30 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 removed. The binding of [³H]MK-801 ([³H](5R,10S)-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5,10-imine) and [³H]CGP 39653 ([³H]d,l-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid) to NMDA receptors in different cortical areas, as well as the binding of [³H]spiperone to dopamine D₂ receptors in the striatum, were analysed by quantitative autoradiography. Haloperidol increased the binding of [³H]CGP 39653 in frontal, insular and parietal cortices. Clozapine increased the binding of [³H]CGP 39653 in insular and parietal cortices. Haloperidol, but not clozapine, increased the binding of [³H]spiperone in the striatum. None of the neuroleptics influenced the binding of [³H]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 [³H]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 regions. Received: 15 September 1998 / Accepted: 25 January 1999