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.
Chowdhury
Golam M I
GM
Department of Diagnostic Radiology, Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, Connecticut, USA. golam.chowdhury@yale.edu
Banasr
Mounira
M
de Graaf
Robin A
RA
Rothman
Douglas L
DL
Behar
Kevin L
KL
Sanacora
Gerard
G
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019782:Riluzole / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D013997:Time Factors
D000596:Amino Acids; D001786:Blood Glucose; D018696:Neuroprotective Agents; D019782:Riluzole; D005947:Glucose