The Steroidogenesis Inhibitor Finasteride Reduces the Response to Both Stressful and Rewarding Stimuli
by
Sean C. Godar 1,†, Roberto Cadeddu 1,†, Gabriele Floris 1, Laura J. Mosher 1,2, Zhen Mi 2, David P. Jarmolowicz 3,4, Simona Scheggi 1, Alicia A. Walf 5,6, Carolyn J. Koonce 6, Cheryl A. Frye 6,7,8,9, Nancy A. Muma 2 and Marco Bortolato 1,*
Sean C. Godar 1,†, Roberto Cadeddu 1,†, Gabriele Floris 1, Laura J. Mosher 1,2, Zhen Mi 2, David P. Jarmolowicz 3,4, Simona Scheggi 1, Alicia A. Walf 5,6, Carolyn J. Koonce 6, Cheryl A. Frye 6,7,8,9, Nancy A. Muma 2 and Marco Bortolato 1,*
1
Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake, UT 84112, USA
2
Department of Pharmacology and Toxicology, School of Pharmacy; Lawrence, KS 66045, USA
3
Department of Applied Behavioral Science; University of Kansas, Lawrence, KS 66045, USA
4
Cofrin Logan Center for Addiction Research and Treatment; University of Kansas, Lawrence, KS 66045, USA
5
Department of Cognitive Science, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
6
Department of Psychology; The University at Albany-SUNY, Albany, NY 12222, USA
7
Department of Biological Sciences; The University at Albany-SUNY, Albany, NY 12222, USA
8
Center for Neuroscience, The University at Albany-SUNY, Albany, NY 12222, USA
9
Comprehensive Neuropsychological Services, Albany, NY 12203, USA
*
Author to whom correspondence should be addressed.
†
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)
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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Keywords:
5α reductase; depression; anxiety; impulsivity; finasteride; HPA axis
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MDPI and ACS Style
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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