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.

Regulation of ionotropic glutamate receptors in the rat brain in response to the atypical antipsychotic seroquel (quetiapine fumarate) / F. Tascedda, E. Lovati, J.M. Blom, P. Muzzioli, N. Brunello, G. Racagni, M.A. Riva. - In: NEUROPSYCHOPHARMACOLOGY. - ISSN 0893-133X. - 21:2(1999 Aug), pp. 211-217. [10.1016/S0893-133X(99)00034-2]

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

G. Racagni
Penultimo
;
M.A. Riva
Ultimo
1999-08

Abstract

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.
Animals; Hippocampus; Brain; Corpus Striatum; Transcription, Genetic; Antipsychotic Agents; Haloperidol; RNA, Messenger; Rats; Dibenzothiazepines; Rats, Sprague-Dawley; Nucleus Accumbens; Clozapine; Receptors, AMPA; Gene Expression Regulation; Receptors, N-Methyl-D-Aspartate; Male
Settore BIO/14 - Farmacologia
http://www.nature.com/npp/journal/v21/n2/full/1395358a.html
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/182762
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