Role of hippocampal p11 in the sustained antidepressant effect of ketamine in the chronic unpredictable mild stress model
Translational Psychiatry February 23, 2016 H-L Sun, Z-Q Zhou, G.-F. Zhang et al. 87 citations
Ketamine produces rapid (within 0.5 hour) and sustained (up to 72 hours) antidepressant effects in rats exposed to chronic unpredictable mild stress (CUMS), a model of depression. The antidepressant action is blocked by ANA-12, a TrkB antagonist, indicating involvement of TrkB signaling. Ketamine restores reduced levels of brain-derived neurotrophic factor (BDNF) in the hippocampus and increases the ratio of phosphorylated TrkB to total TrkB. While ketamine does not affect p11 expression shortly after administration, it normalizes reduced p11 and BDNF levels 72 hours later. Knockdown of hippocampal p11 prevents ketamine's behavioral effects, suggesting p11 is essential for the sustained antidepressant response.