Depression is a common mental disorder that is associated with memory dysfunction.Ketamine has recently been demonstrated to be a rapid antidepressant.The mechanisms underlying how depression induces memory dysfunction and how ketamine relieves depressive symptoms remain poorly understood.This work compared three groups of male C57BL/6J mice: mice exposed to chronic social defeat stress (CSDS) to induce a depression-like phenotype, depression-like mice treated with ketamine, and control mice that were not exposed to CSDS or treated with Gun Care ketamine.
Spatial working memory and long term memory were assessed by spontaneous alternation Y-maze and fear conditioning tests, respectively.We used western blot to analyze the density of N-methyl-D-aspartate receptor (NMDAR) subunits in the hippocampus.We recorded long term potentiation (LTP) and NMDA receptor-mediated excitatory postsynaptic currents (EPSCs) in hippocampal slices.We observed that compared with control mice, depression-like mice had significant reductions in spatial working memory and contextual fear memory.
The level of NR2B, LTP and NMDA receptor-mediated EPSCs of depression-like mice were decreased.Ketamine treatment attenuated the memory impairment, and increased the density of NR2B and the amplitude of LTP and NMDA receptor-mediated EPSCs in the hippocampus of depression-like mice.In conclusion, depression-like mice have deficits in working memory and contextual fear memory.The decrease of NR2B, LTP induction and NMDA receptor-mediated EPSCs in the hippocampus may be involved in this process.
Ketamine can improve expression of NR2B, LTP induction and NMDA receptor-mediated EPSCs in the hippocampus of depression-like mice, which might be part of the reason why ketamine can alleviate the memory Pram Clip dysfunction induced by depression.