Zhang J, Qu Y, Chang L, Pu Y, Hashimoto K. (R)-Ketamine Rapidly Ameliorates the Decreased Spine Density in the Medial Prefrontal Cortex and Hippocampus of Susceptible Mice After Chronic Social Defeat Stress. Int J Neuropsychopharmacol. 2019 Oct 1;22(10):675-679. doi: 10.1093/ijnp/pyz048. PMID: 31504547; PMCID: PMC6822137.
Highlights:
- 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.
- 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.
Results:
Dendritic spine densities in the PrL regions of the mPFC, CA3, and DG of the hippocampus from susceptible mice were significantly lower than those from control mice, consistent with previous reports (Figure 2A, ,D,D, andandE;E; Yang et al., 2015; Dong et al., 2017; Qu et al., 2018). In contrast, spine densities in the IL regions of the mPFC and CA1 of the hippocampus from susceptible mice were not different from those in control mice, consistent with previous reports (Figure 2B and andC;C; Yang et al., 2015; Dong et al., 2017; Qu et al., 2018). A single injection of (R)-ketamine (10 mg/kg at 3 h post-treatment) significantly ameliorated the decreased spine densities in the PrL areas of the mPFC, CA3, and DG of the hippocampus from susceptible mice (Figure 2A, ,D,D, andandEE).”
Conclusion:
In conclusion, this study indicates that (R)-ketamine rapidly (<3 h) ameliorates the decreased spine densities in the PrL regions of the mPFC, CA3, and DG in susceptible mice after CSDS, suggesting this mechanism for its rapid-acting antidepressant effects. Further detailed study using single-cell 2-photon calcium imaging is needed to confirm the acute effects of ketamine and its enantiomers for spine formation in rodents with depression-like phenotypes.
