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

Biomolecules

DavidP. Jarmolowicz¹  Marco Bortolato²  AliciaA. Walf³  Simona Scheggi⁴  CherylA. Frye⁵  Gabriele Floris⁶  CarolynJ. Koonce⁶  LauraJ. Mosher⁶  SeanC. Godar⁶  Roberto Cadeddu⁶  Zhen Mi⁷  NancyA. Muma⁸ 

[1] Lawrence, KS 66045, USA;The University at Albany-SUNY, Albany, NY 12222, USA;University of Kansas, Lawrence, KS 66045, USA;Department of Applied Behavioral Science;Department of Cognitive Science, Rensselaer Polytechnic Institute, Troy, NY 12180, USA;Department of Pharmacology and Toxicology, College of Pharmacy, University of Utah, Salt Lake, UT 84112, USA;Department of Pharmacology and Toxicology, School of Pharmacy;Department of Psychology;

关键词: 5α reductase;    depression;    anxiety;    impulsivity;    finasteride;    hpa axis;   

DOI  :  10.3390/biom9110749

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown