F. Tascedda et al., Regulation of ionotropic glutamate receptors in the rat brain in response to the atypical antipsychotic Seroquel (quetiapine fumarate), NEUROPSYCH, 21(2), 1999, pp. 211-217
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.