Subanesthetic ketamine reverses neuronal and astroglial metabolic activity deficits in a social defeat model of depression

Depression is one of the most debilitating neuropsychiatric disorders. Most of the current antidepressants have long remission time and low recovery rate. This study explores the impact of ketamine on neuronal and astroglial metabolic activity in prefrontal cortex in a social defeat (SD) model of depression. C57BL/6 mice were subjected to a social defeat paradigm for 5 min a day for 10 consecutive days. Ketamine (10 mg/kg, intraperitoneal) was administered to mice for two consecutive days following the last defeat stress. Mice were infused with [1,6‐¹³C₂]glucose or [2‐¹³C]acetate to assess neuronal and astroglial metabolic activity, respectively, together with proton‐observed carbon‐edited nuclear magnetic resonance spectroscopy in prefrontal cortex tissue extract. The ¹³C labeling of amino acids from glucose and acetate was decreased in SD mice. Ketamine treatment in SD mice restored sucrose preference, social interaction and immobility time to control values. Acute subanesthetic ketamine restored the ¹³C labeling of brain amino acids from glucose as well as acetate in SD mice to the respective control values, suggesting that rates of neuronal and astroglial tricarboxylic acid (TCA) cycle and neurotransmitter cycling were re‐established to normal levels. The finding of improved energy metabolism in SD mice suggests that fast anti‐depressant action of ketamine is linked with improved neurotransmitter cycling.