Chronic Riluzole Treatment Increases Glucose Metabolism in Rat Prefrontal Cortex and Hippocampus

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.