Inhibition of Progesterone Metabolism Mimics the Effect of Progesterone Withdrawal on Forced Swim Test Immobility

The study investigated the effects of progesterone withdrawal (PWD) and the 5α-reductase inhibitor finasteride on depression-like behavior in female DBA/2J mice using the forced swim test (FST). It was found that 3 days of PWD increased FST immobility, indicating depression-like behavior, and this effect was mimicked by high doses (100 mg/kg) of finasteride, which inhibits progesterone metabolism. The results suggested that reduced levels of the neurosteroid allopregnanolone, a product of progesterone metabolism, contributed to these behaviors. These findings provided insights into how hormonal changes might relate to conditions like premenstrual syndrome or postpartum depression.