Progesterone Promotes Anti-Anxiety and Antidepressant-Like Behavior and Trophic Actions of BDNF in the Hippocampus of Female Nuclear Progesterone Receptor, but Not 5α-Reductase, Knockout Mice

The study examines the effects of progesterone (P4) and its metabolite allopregnanolone on anxiety and depression-like behaviors in female mice, focusing on the roles of nuclear progesterone receptors (NPRs) and 5α-reductase. Using 320 mice, including wildtype, 5α-reductase knockout, and progesterone receptor knockout strains, the research found that P4's anti-anxiety and anti-depressant effects are independent of NPRs but require 5α-reduction and brain-derived neurotrophic factor (BDNF) actions in the hippocampus. Allopregnanolone enhances neuroplasticity, suggesting potential therapeutic applications for mood disorders. The study underscores the significance of hormonal pathways in mood regulation and the potential of allopregnanolone as a pharmacological tool.