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 investigates the anti-anxiety and anti-depressive effects of progestogens, focusing on the role of progesterone (P4) and its neuroactive metabolite allopregnanolone (3α,5α-THP) in female mice. Results indicate that adult female mice exhibit anti-anxiety and anti-depressant-like behaviors when administered P4, with these effects being independent of nuclear progestin receptors but requiring 5α-reduction and estradiol (E2) priming. The study involved c57 and 5α-reductase knockout (5αRKO) mice, showing that P4 and 3α,5α-THP increase central entries in an open field, indicating reduced anxiety. Additionally, P4 decreased depression-like behavior in a forced swim task. The findings suggest that the effects of P4 are linked to increased levels of brain-derived neurotrophic factor (BDNF) in the hippocampus/amygdala, highlighting the importance of 5α-reduction and E2 in modulating these behaviors.