Golam M.I. Chowdhury1, Mounira Banasr2, Kevin L. Behar1, Gerard Sanacora3
1Department of Psychiatry and Magnetic Resonance Research Center, Yale University School of Medicine, New Haven, CT, United States; 2Department of Psychiatry, Yale University School of Medicine, New Haven, CT, United States; 3Department of Psychiatry and the Ribicoff Research Facilities, , Yale University School of Medicine, New Haven, CT, United States
We investigated the effects of riluzole, a drug shown enhance of glial glutamate clearance and modulate presynaptic glutamate release, and ceftriaxone, a β-lactam antibiotic known to elevate GLT1 expression, on neuronal and glial metabolism in awake rats subjected to chronic unpredictable stress (CUS), a rodent model of depression, or control conditions. The CUS animals were subjected to 12 stressors (2 per day for 35 days) and riluzole or ceftriaxone was administered once daily for the last 21 days. 13C enrichments of glutamate, GABA and glutamine were measured using 1H-[13C]-NMR spectroscopy at 11.74T in extracts following infusions of either [1-13C]glucose, a substrate metabolized mainly in the neuronal TCA cycle, or [2-13C]acetate, a substrate metabolized by astrocytes labeling glutamine. CUS led to decreased 13C labeling from glucose and acetate suggesting altered neuronal and glial metabolism. Chronic riluzole treatment attenuated stress effects on neuron and glial neurotransmitter uptake/cycling, however, chronic ceftriaxone treatment mainly attenuated the neuronal effects with less prominent effects on glial cell metabolism.