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

• Published in: Journal of cerebral blood flow and metabolism 2008-12, Vol.28 (12), p.1892-1897
• Main Authors: Chowdhury, Golam MI, Banasr, Mounira, de Graaf, Robin A, Rothman, Douglas L, Behar, Kevin L, Sanacora, Gerard
• Format: Article
• Language: English
• Subjects: Amino Acids - metabolism; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Blood Glucose - metabolism; Cardiovascular system; Glucose - metabolism; Hippocampus - drug effects; Hippocampus - metabolism; Male; Medical sciences; Neurology; Neuroprotective Agents - administration & dosage; Neuroprotective Agents - pharmacokinetics; Neuroprotective Agents - pharmacology; Pharmacology. Drug treatments; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Rats; Rats, Sprague-Dawley; Riluzole - administration & dosage; Riluzole - pharmacokinetics; Riluzole - pharmacology; Time Factors; Vascular diseases and vascular malformations of the nervous system; Vasodilator agents. Cerebral vasodilators
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.2008.78

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.