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 C-13 labeling in metabolites in prefrontal cortex and hippocampus during a 10 mins infusion of [1-C-13] glucose in urethane anesthetized rats treated with riluzole (21 days, 4 mg/kg per day, i.p.) or saline. Total and C-13 concentrations of metabolites were determined in extracts using H-1-[C-13] NMR spectroscopy. In prefrontal cortex (P < 0.05) and hippocampus (P < 0.05) riluzole increased C-13 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.