Examining the Effect of Ketamine on Glutamate/Glutamine Cycling

Ketamine is an FDA-approved anesthetic agent that has been found to produce rapid and potent antidepressant effects in individuals with severe depression. Mounting evidence suggests ketamine administration produces a surge in glutamate neurotransmission in the brain, that is likely associated with the antidepressant effects (as well as some of the side-effects of the medication). Until recently, we have been unable to examine glutamate neurotransmission in human participants because we lacked appropriate and safe methods to do so. This study uses new, state-of-the-art neuroimaging methods to measure the effect of ketamine on glutamate/glutamine neurotransmission in the brain. It is suspected that ketamine will cause a significant increase in the rate of neurotransmission and that these changes will correlate to antidepressant effects. The results of this study can help to inform how ketamine works in the brain and how glutamate neurotransmission may be related to changes in depressive symptoms, which can inform novel drug development.

This study involves four neuroimaging scan visits. Two of these visits will use MRI methods to evaluate the structure and function of the brain. Two visits will use a novel imaging method called carbon 13 magnetic resonance spectroscopy. Briefly, we use glucose or acetate (a naturally occurring and safe substance the brain uses for energy like glucose) with the carbon 13 molecules labeled. This allows us to monitor how the glucose/acetate is metabolized in the brain and to investigate how this is influenced by ketamine. We complete structural/functional scans before and after ketamine administration.