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Long-term Treatment with a 5-Alpha-Reductase Inhibitor Alleviates Depression-like Behavior in Obese Male Rats.

Thiraphat Saengmearnuparp1, Hiranya Pintana2, Nattayaporn Apaijai3

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Behavioural Brain Research
|July 20, 2024
PubMed
Summary

Long-term finasteride (FIN) treatment and withdrawal in lean rats worsened anxiety and depression. However, in obese rats, FIN showed potential benefits by reducing depressive behaviors and brain inflammation.

Keywords:
Brain tryptophan-kynurenine pathwayDepressionFinasterideInflammationObesity

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Area of Science:

  • Neuroscience
  • Endocrinology
  • Metabolic Syndrome

Background:

  • Finasteride (FIN) is linked to anxiety/depression, particularly in young men.
  • Obesity exacerbates anxiety/depression; however, FIN's long-term effects and withdrawal impact in obese individuals remain unclear.

Purpose of the Study:

  • To investigate the effects of long-term FIN treatment and its withdrawal on anxiety/depression and brain pathologies in lean and obese rats.

Main Methods:

  • Adult male Wistar rats were fed normal or high-fat diets, then treated with FIN (5 mg/kg/day) for 6 weeks or FIN for 2 weeks followed by 4 weeks of withdrawal.
  • Evaluated anxiety/depression behaviors, brain inflammation, oxidative stress, neuroactive steroids, metabolites, and microglial complexity.

Main Results:

  • Lean rats on FIN (long-term or withdrawal) showed metabolic issues, depressive behavior, increased neurotoxic metabolites, and reduced microglial complexity.
  • Obesity induced metabolic disturbances, brain pathologies (inflammation, oxidative stress, quinolinic acid), and anxiety/depression-like behaviors.
  • Obese rats receiving long-term FIN exhibited reduced depressive behavior, brain inflammation, and oxidative stress, with increased brain antioxidants.

Conclusions:

  • Long-term FIN and withdrawal negatively impact lean rats' mental health and brain structure.
  • Obesity itself drives significant neuroinflammation and behavioral deficits.
  • Finasteride may offer neuroprotective benefits in obese individuals, attenuating depressive symptoms and brain pathology.