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  • Title: Clozapine reduces GLT-1 expression and glutamate uptake in astrocyte cultures.
    Author: Vallejo-Illarramendi A, Torres-Ramos M, Melone M, Conti F, Matute C.
    Journal: Glia; 2005 May; 50(3):276-9. PubMed ID: 15739191.
    Abstract:
    To test the hypothesis that clozapine-induced reduction of glutamate transporter-1 (GLT-1) expression is mediated by astrocytes, we studied the effects of clozapine on Glu transporters and Glu uptake in primary astrocyte cultures of the cerebral cortex. Astrocyte cultures treated for 48 h with clozapine exhibited a reduction in GLT-1 levels of about 50%, whereas glutamate-aspartate transporter (GLAST) levels remained unchanged. Glu uptake was also lowered, and this reduction was dose-dependent. Our findings indicate that clozapine reduces GLT-1 expression and function by a mechanism that directly involves astrocytes. A better understanding of the molecular events by which antipsychotics regulate Glu uptake can contribute to identify new targets for the treatment of schizophrenia.
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