Regulation of ionotropic glutamate receptors in the rat brain in response to the atypical antipsychotic Seroquel (quetiapine fumarate)

The interplay between dopamine and glutamate appears to be relevant in the etiopathology of schizophrenia. Although currently used antipsychotics do n ot interact with glutamatergic receptors, previous results have demonstrate d that the expression profile of ionotropic glutamate receptors can be regu lated by drugs such as haloperidol or clozapine. In the present investigati on, the mRNA levels for NMDA and AMPA receptor subunits were measured after chronic treatment with the novel antipsychotic agent Seroquel (quetiapine fumarate, quetiapine) as compared to haloperidol and clozapine. Similarly t o the prototype atypical clozapine, quetiapine reduced the mRNA expression for NR-I and NR-2C, two NMDA forming subunits, in the nucleus accumbens. Fu rthermore, quetiapine, but Mot haloperidol or clozapine, increased the hipp ocampal Expression for the AMPA subunits GluR-B and GluR-C. The differences between classical and atypical antipsychotics, as well as among the novel agents, might be relevant for specific aspects of their therapeutic activit y and could provide valuable information for the role of glutamate in speci fic symptoms of schizophrenia. (C) 1999 American College of Neuropsychophar macology. Published by Elsevier Science Inc.