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Clozapine-induced reduction of glutamate transport in the frontal cortex is not mediated by GLAST and EAAC1

Molecular Psychiatry volume 8, pages 12–13 (2003)Cite this article

SIR – Glutamate (Glu), the main excitatory neurotransmitter in the cerebral cortex, has been implicated in several neuropsychiatric disorders, including schizophrenia.1 The effects of Glu are determined, among others, by the action of high-affinity Glu transporters (GluTs).2 To date, five GluTs have been characterized: GLT-1, GLAST, EAAC1, EAAT4, and EAAT5.2,3

Clozapine, a highly effective antipsychotic,4 increases the extracellular levels of Glu in the rat frontal cortex.5,6 Recently, we showed that clozapine reduces cortical expression of GLT-1 and decreases total Glu uptake by 60% in the rat frontal cortex,6 suggesting that the clozapine-induced increase in Glu levels depends on GLT-1 down-regulation. In the neocortex, EAAT4 and EAAT5 expression is poor or absent3 and therefore their contribution to total cortical Glu uptake is extremely small, whereas GLAST and EAAC1 are robustly expressed7,8 and mediate a sizeable fraction of total Glu uptake.9 Whether the expression of GLAST and EAAC1 is altered by clozapine is unknown.

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References

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Authors and Affiliations

  1. Istituto di Fisiologia Umana, Università di Ancona, Via Tronto 10/A, Torrette di Ancona, Ancona, 60020, Italy

    M Melone, L Bragina & F Conti

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  1. M Melone
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  2. L Bragina
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  3. F Conti
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Correspondence to F Conti.

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Supported by a Stanley Foundation Award.

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Melone, M., Bragina, L. & Conti, F. Clozapine-induced reduction of glutamate transport in the frontal cortex is not mediated by GLAST and EAAC1. Mol Psychiatry 8, 12–13 (2003). https://doi.org/10.1038/sj.mp.4001193

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