Lack of effect of ketamine on cortical glutamate and glutamine in healthy volunteers: a proton magnetic resonance spectroscopy study

Ketamine is a N-methyl-D-aspartic acid (NMDA) antagonist that has been associated with temporary clinical improvement in patients with depression. Studies using magnetic resonance spectroscopy (MRS) have shown that major depression is associated with decreased levels of glutamate and glutamine (Glx) in the anterior cingulate cortex, which normalize with clinical recovery. The present study aimed to test whether a ketamine infusion would increase cortical Glx levels in healthy volunteers. Healthy volunteers received an intravenous infusion of ketamine (0.5 mg kg-1, n = 8) or saline (n = 9) over 40 minutes. MRS measurements were obtained at baseline, during, and at the end of the infusion. The infusion of ketamine had significant effects on mental state but there was no effect of ketamine on the levels of Glx (F3,39 = 1.70, p = 0.18) or glutamate (F3,39 = 48, p = 0.70). This study suggests that the gradual infusion of low-dose ketamine in antidepressant doses not cause changes in cortical glutamate or glutamine in healthy volunteers that are visible by proton MRS.