Introduction: Major Depressive Disorder (MDD) is a prominent, debilitating global health concern. An estimated 53% of patients with MDD do not respond to first-line treatment (1). Of those that do respond, roughly 67% do not experience remission (1). Clearly, more effective treatment options for MDD are needed. As a proven protective factor against MDD (2-4), the neurobiological basis of resilience is of significant interest in the research and development of novel MDD therapies. Many critical aspects of both depression pathophysiology and resilience neurobiology are regulated by steroid hormones synthesized by the brain called neurosteroids (5-8).
Hypothesis: Administration of the neurosteroid allopregnanolone in adolescent mice with a pharmacologically or genetically induced depressive phenotype will improve observed symptoms of depression better than monotherapy with the first-line antidepressant fluoxetine.
Study Design: one-way ANOVA experimental animal study
Methods: C57BL6/J mice were injected with either finasteride (25 mg/kg, IP) or vehicle, followed by either fluoxetine (15 mg/kg, IP) or vehicle 15 minutes later. All mice were subjected to a 5-minute Forced Swim Test (FST) 45 minutes after the initial finasteride or vehicle injection.
Results: We expect increased immobility times during the FST from mice treated with finasteride. We expect a decrease in total immobility time for mice subsequently treated with allopregnanolone compared to those treated with fluoxetine.
Conclusions: Due to the fact that reduced 5alphaR brain levels are directly correlated with chronic psychosocial stress and depression (9, 10), circumvention of these low enzyme levels via replenishment of their metabolized neurosteroids is a promising therapeutic target for the treatment of MDD.Published in