Changes in Progesterone Metabolites in the Hippocampus Can Modulate Open Field and Forced Swim Test Behavior of Proestrous Rats

The study tested the hypothesis that reducing the 5α-reduced progesterone metabolite 3α,5α-THP in the hippocampus would affect anxiety and depression behaviors in proestrous rats. Proestrous rats, with naturally higher levels of 3α,5α-THP, showed more anxiolytic and anti-depressant behaviors compared to diestrous and male rats. Experiments using finasteride, a 5α-reductase inhibitor, demonstrated that reducing 3α,5α-THP levels led to increased anxiety and depression-like behaviors, as evidenced by decreased central entries in the open field and increased immobility in the forced swim test. These findings suggested that 3α,5α-THP levels in the hippocampus played a role in modulating anxiety and depressive behaviors in proestrous rats.