Role of ERα in Ketamine’s Effects

In this study, we investigated the role of ERα in the heightened sensitivity of female animals to ketamine’s antidepressant effects. This well-documented sex difference is thought to stem from the faster ketamine metabolism observed in females, potentially regulated by ERα through enzymatic modulation. However, our results indicate that ERα antagonism did not influence behavioral despair in the FST. An interaction between MPP and ketamine emerged in anxiety-like behaviors assessed in the OFT and EPM, though post-hoc analyses did not reveal significant effects. Neither MPP nor ketamine affected fear memory, as measured in cued fear conditioning. These findings suggest that ketamine’s sexually dimorphic antidepressant effects occur independently of ERα activity, though ERα may play a role in neural circuits underlying anxiety.

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