The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli
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Issue Date
2019-11-19Author
Godar, Sean C.
Cadeddu, Roberto
Floris, Gabriele
Mosher, Laura J.
Mi, Zhen
Jarmolowicz, David P.
Scheggi, Simona
Walf, Alicia A.
Koonce, Carolyn J.
Frye, Cheryl A.
Muma, Nancy A.
Bortolato, Marco
Publisher
MDPI
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
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Show full item recordAbstract
Finasteride (FIN) is the prototypical inhibitor of steroid 5α-reductase (5αR), the enzyme that catalyzes the rate-limiting step of the conversion of progesterone and testosterone into their main neuroactive metabolites. FIN is clinically approved for the treatment of benign prostatic hyperplasia and male baldness; while often well-tolerated, FIN has also been shown to cause or exacerbate psychological problems in vulnerable subjects. Evidence on the psychological effects of FIN, however, remains controversial, in view of inconsistent clinical reports. Here, we tested the effects of FIN in a battery of tests aimed at capturing complementary aspects of mood regulation and stress reactivity in rats. FIN reduced exploratory, incentive, prosocial, and risk-taking behavior; furthermore, it decreased stress coping, as revealed by increased immobility in the forced-swim test (FST). This last effect was also observed in female and orchiectomized male rats, suggesting that the mechanism of action of FIN does not primarily reflect changes in gonadal steroids. The effects of FIN on FST responses were associated with a dramatic decrease in corticotropin release hormone (CRH) mRNA and adrenocorticotropic hormone (ACTH) levels. These results suggest that FIN impairs stress reactivity and reduces behavioral activation and impulsive behavior by altering the function of the hypothalamus–pituitary–adrenal (HPA) axis.
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This work is licensed under a Creative Commons Attribution 4.0 International License.
Collections
- Pharmacy Scholarly Works [293]
Citation
Godar, S.C.; Cadeddu, R.; Floris, G.; Mosher, L.J.; Mi, Z.; Jarmolowicz, D.P.; Scheggi, S.; Walf, A.A.; Koonce, C.J.; Frye, C.A.; Muma, N.A.; Bortolato, M. The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli. Biomolecules 2019, 9, 749.
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