(R)-Ketamine Rapidly Ameliorates the Decreased Spine Density in the Medial Prefrontal Cortex and Hippocampus of Susceptible Mice After Chronic Social Defeat Stress

Summary

A single injection of (R)-ketamine (10 mg/kg) rapidly reversed the loss of dendritic spines in the medial prefrontal cortex and hippocampus of mice that had become susceptible after chronic social defeat stress. Spine density was measured three hours after treatment and was significantly increased in the prelimbic area of the medial prefrontal cortex, the Cornu Ammonis3 region, and the dentate gyrus of the hippocampus. The findings suggest that (R)-ketamine's rapid restoration of spine density in these brain regions may underlie its fast-acting antidepressant effects.

Study at a glance

Abstract

BACKGROUND: A recent study demonstrated that spine formation rates by ketamine in the prefrontal cortex (PFC) were not altered at 3-6 h following a single injection, but were markedly altered at 12-24 h. Here, we investigated the acute (3 h post-treatment) effects of (R)-ketamine in the decreased spine density in the medial PFC (mPFC) and hippocampus in susceptible mice after chronic social defeat stress (CSDS). METHODS: (R)-ketamine (10 mg/kg) or saline was administered intraperitoneally to CSDS-susceptible mice. Dendritic spine density in the mPFC and hippocampus was measured 3 h after a single injection. RESULTS: (R)-ketamine significantly ameliorated the decreased spine density in the prelimbic area of mPFC, Cornu Ammonis3, and dentate gyrus of the hippocampus of CSDS-susceptible mice. CONCLUSIONS: This study suggests that (R)-ketamine rapidly ameliorates the decreased spine density in the mPFC and hippocampus of CSDS-susceptible mice, resulting in its rapid-acting antidepressant effects.