Sex Differences in the Antidepressant Effects of Ketamine

Abstract

Major depressive disorder (MDD) is a disabling mental disorder characterized by negative mood and suicidality. The NMDA antagonist ketamine has been found to reduce depressive symptoms and suicidal thoughts in patients unresponsive to first-line antidepressants, but ketamine's mechanism of action remains unclear.More women are diagnosed with MDD than men and present with greater suicidal ideation, but it is unclear if there are sex-dependent responses to ketamine.It was recently determined that activating mRNA translation via phosphorylation of the eukaryotic initiation factor 4E binding proteins (4E-BPs) is a crucial mechanism of ketamine's antidepressant effect in non-stressed male mice. The aim is to understand if stressed females also engage this mechanism following ketamine treatment. After investigating whether 4E-BP1 and 4E-BP2 are relevant to ketamine's antidepressant mechanisms of action in female mice, the present study's findings are inconclusive, as ketamine had no effect on several chronic variable stress-induced behaviors in tested mice.