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-10,1 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 Bmax 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.
Ossowska
K
K
Department of Neuro-Psychopharmacology, Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. ossowska@if-pan.krakow.pl
Pietraszek
M
M
Wardas
J
J
Nowak
G
G
Wolfarth
S
S
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000378:metabolism; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001345:Autoradiography; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D014316:Tritium
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; C069052:CGP 39653; D013134:Spiperone; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D003024:Clozapine; D006220:Haloperidol