Brief Communication

Journal of Cerebral Blood Flow & Metabolism (2008) 28, 1892–1897; doi:10.1038/jcbfm.2008.78; published online 16 July 2008

Chronic riluzole treatment increases glucose metabolism in rat prefrontal cortex and hippocampus

This work was supported in part by grants from the National Institutes of Health, NIMH 1K02 MH076222 (GS), NIMH R01 MH071676 (GS), NIDDK R01 DK027121 (KB), NINDS 1 P30 NS052519 for spectrometer support, and a NARSAD Independent Investigator Award (GS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or NARSAD.

Golam M I Chowdhury1, Mounira Banasr2, Robin A de Graaf1, Douglas L Rothman1, Kevin L Behar2 and Gerard Sanacora2

  1. 1Department of Diagnostic Radiology, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut, USA
  2. 2Department of Psychiatry, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut, USA

Correspondence: Dr GMI Chowdhury, Department of Diagnostic Radiology, Magnetic Resonance Research Center, Yale University School of Medicine, TAC-MRRC, N144, PO Box 208043, 300 Cedar Street, New Haven, CT 6510, USA. E-mail: golam.chowdhury@yale.edu

Received 19 February 2008; Revised 19 June 2008; Accepted 20 June 2008; Published online 16 July 2008.

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Abstract

Riluzole is believed to modulate glutamatergic function by reducing glutamate release and facilitating astroglial uptake. We measured 13C labeling in metabolites in prefrontal cortex and hippocampus during a 10 mins infusion of [1-13C]glucose in urethane anesthetized rats treated with riluzole (21 days, 4 mg/kg per day, i.p.) or saline. Total and 13C concentrations of metabolites were determined in extracts using 1H-[13C] NMR spectroscopy. In prefrontal cortex (P<0.05) and hippocampus (P<0.05) riluzole increased 13C labeling over saline in glutamate-C4 (to 112% and 130%), GABA-C2 (to 142% and 171%), and glutamine-C4 (to 118% and 233%) without affecting total metabolite levels (P>0.2). Our findings indicate that contrary to expectation chronic riluzole enhanced glucose oxidative metabolism and glutamate/glutamine cycling.

Keywords:

glutamate, GABA, glutamine, TCA cycle, riluzole, nuclear magnetic resonance spectroscopy

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