The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli

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

doi:10.3390/biom9110749

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The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli

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Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake, UT 84112, USA

Department of Pharmacology and Toxicology, School of Pharmacy; Lawrence, KS 66045, USA

Department of Applied Behavioral Science; University of Kansas, Lawrence, KS 66045, USA

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Cofrin Logan Center for Addiction Research and Treatment; University of Kansas, Lawrence, KS 66045, USA

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Department of Cognitive Science, Rensselaer Polytechnic Institute, Troy, NY 12180, USA

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Department of Psychology; The University at Albany-SUNY, Albany, NY 12222, USA

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Department of Biological Sciences; The University at Albany-SUNY, Albany, NY 12222, USA

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Center for Neuroscience, The University at Albany-SUNY, Albany, NY 12222, USA

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Comprehensive Neuropsychological Services, Albany, NY 12203, USA

Author to whom correspondence should be addressed.

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These authors contributed equally to this work.

Biomolecules 2019, 9(11), 749; https://doi.org/10.3390/biom9110749

Received: 14 October 2019 / Revised: 14 November 2019 / Accepted: 18 November 2019 / Published: 19 November 2019

(This article belongs to the Special Issue Bioactive Lipids in Health and Disease)

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Abstract

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. View Full-Text

Keywords: 5α reductase; depression; anxiety; impulsivity; finasteride; HPA axis

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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. https://doi.org/10.3390/biom9110749

AMA Style

Godar SC, Cadeddu R, Floris G, Mosher LJ, Mi Z, Jarmolowicz DP, Scheggi S, Walf AA, Koonce CJ, Frye CA, Muma NA, Bortolato M. The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli. Biomolecules. 2019; 9(11):749. https://doi.org/10.3390/biom9110749

Chicago/Turabian Style

Godar, Sean C., Roberto Cadeddu, Gabriele Floris, Laura J. Mosher, Zhen Mi, David P. Jarmolowicz, Simona Scheggi, Alicia A. Walf, Carolyn J. Koonce, Cheryl A. Frye, Nancy A. Muma, and Marco Bortolato. 2019. "The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli" Biomolecules 9, no. 11: 749. https://doi.org/10.3390/biom9110749

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The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli

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