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

Riluzole is believed to modulate glutamatergic function by reducing glutamate release and facilitating astroglial uptake. We measured (13)C labeling in metabolites in prefrontal cortex and hippocampus during a 10 mins infusion of [1-(13)C]glucose in urethane anesthetized rats treated with riluzole (21 days, 4 mg/kg per day, i.p.) or saline. Total and (13)C concentrations of metabolites were determined in extracts using (1)H-[(13)C] NMR spectroscopy. In prefrontal cortex (P<0.05) and hippocampus (P<0.05) riluzole increased (13)C 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.