Long-term ketamine usage affects mood, cognition, and neurometabolism in mice

Motivation: Recently FDA has approved S-ketamine for the treatment of drug-resistant depression. However, the impact of long-term use of ketamine on mood, cognition, and neurotransmitter pathways is not clear. Goal(s): To assess the impacts of chronic ketamine administration on mood, cognition, and neurometabolism in the mice model. Approach: 1H-[13C]-NMR spectroscopy in conjunction with an intravenous [1,6-13C2]glucose infusion was used for neurometabolic measurements. Results: Ketamine administered mice showed hyperactivity, reduced cognition, and depression-like phenotypes. Moreover, chronic ketamine exposure increased the metabolic activity of glutamatergic and GABAergic neurons in the cerebral cortex. Impact: Ketamine, a rapid-acting antidepressant, has been abused as a party drug historically. This study was performed to uncover the adverse effects of chronic ketamine administration and will be useful in designing better treatment approaches for depression.