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.