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The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder
Gabriel D. Bosse, … , Marco Bortolato, Randall T. Peterson
Gabriel D. Bosse, … , Marco Bortolato, Randall T. Peterson
Published April 13, 2021
Citation Information: J Clin Invest. 2021;131(10):e143990. https://doi.org/10.1172/JCI143990.
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Research Article Neuroscience Article has an altmetric score of 25

The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder

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Abstract

Opioid use disorder (OUD) has become a leading cause of death in the United States, yet current therapeutic strategies remain highly inadequate. To identify potential treatments for OUD, we screened a targeted selection of over 100 drugs using a recently developed opioid self-administration assay in zebrafish. This paradigm showed that finasteride, a steroidogenesis inhibitor approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia, reduced self-administration of multiple opioids without affecting locomotion or feeding behavior. These findings were confirmed in rats; furthermore, finasteride reduced the physical signs associated with opioid withdrawal. In rat models of neuropathic pain, finasteride did not alter the antinociceptive effect of opioids and reduced withdrawal-induced hyperalgesia. Steroidomic analyses of the brains of fish treated with finasteride revealed a significant increase in dehydroepiandrosterone sulfate (DHEAS). Treatment with precursors of DHEAS reduced opioid self-administration in zebrafish in a fashion akin to the effects of finasteride. These results highlight the importance of steroidogenic pathways as a rich source of therapeutic targets for OUD and point to the potential of finasteride as a new treatment option for this disorder.

Authors

Gabriel D. Bosse, Roberto Cadeddu, Gabriele Floris, Ryan D. Farero, Eva Vigato, Suhjung J. Lee, Tejia Zhang, Nilesh W. Gaikwad, Kristen A. Keefe, Paul E.M. Phillips, Marco Bortolato, Randall T. Peterson

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Figure 3

Finasteride treatment reduces opioid self-administration in rats.

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Finasteride treatment reduces opioid self-administration in rats.
(A) Ra...
(A) Rats were conditioned to self-administer hydrocodone and after establishing robust FR5, they were treated with either vehicle or finasteride. (B) A total of 6 animals per condition were tested with active lever presses for animals trained with different concentrations of hydrocodone. Treatment with finasteride (50 mg/kg) reduced opioid self-administration of hydrocodone for animals conditioned with 0.032 and 0.064 mg/kg. P value was corrected for multiple-comparison 2-way ANOVA [F(1, 38) = 30.5, P = 0.0001]. P value compared finasteride-treated versus vehicle-treated animals *P < 0.05, **P < 0.01. (C) Injection (i.p.) with 50 mg/kg but not 25 mg/kg finasteride reduced the number of active lever presses for 0.064 mg/kg hydrocodone; 8 animals were treated for each dose of finasteride. P values were corrected for multiple comparisons by 1-way ANOVA [F(2, 21) = 4.69, P = 0.02]. Data are shown as the mean ± SEM. Adult male Sprague-Dawley rats were used to perform the hydrocodone self-administration assay. These experiments were performed using a within-subjects design.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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