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 not interact with glutamatergic receptors, previous results have demonstrated that the expression profile of ionotropic glutamate receptors can be regulated by drugs such as haloperidol or clozapine. In the present investigation, 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 to the prototype atypical clozapine, quetiapine reduced the mRNA expression for NR-1 and NR-2C, two NMDA forming subunits, in the nucleus accumbens. Furthermore, quetiapine, but not haloperidol or clozapine, increased the hippocampal 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 activity and could provide valuable information for the role of glutamate in specific symptoms of schizophrenia.
Tascedda
F
F
Center for Neuropharmacology, Institute of Pharmacological Sciences, University of Milan, Italy.
Lovati
E
E
Blom
J M
JM
Muzzioli
P
P
Brunello
N
N
Racagni
G
G
Riva
M A
MA
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000378:metabolism*; D003024:Clozapine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D003987:Dibenzothiazepines / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006220:Haloperidol / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000378:metabolism; D000069348:Quetiapine Fumarate; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D012333:RNA, Messenger; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D000069348:Quetiapine Fumarate; D003024:Clozapine; D006220:Haloperidol