The 5α-reductase inhibitor finasteride reduces opioid self-administration

Bosse, G. D.; Cadeddu, R.; Floris, G.; Farero, R.; Vigato, E.; Lee, J.; Zhang, T.; Gaikwad, N.; Keefe, K.; Phillips, P. E. M.; Bortolato, M.; Peterson, R. T.

doi:10.1101/2020.09.15.291609

bioRxiv · 10.1101/2020.09.15.291609

The 5α-reductase inhibitor finasteride reduces opioid self-administration

Bosse, G. D.·Cadeddu, R.·Floris, G.·Farero, R.·Vigato, E.·Lee, J.·Zhang, T.·Gaikwad, N.·Keefe, K.·Phillips, P. E. M.·Bortolato, M.·Peterson, R. T.

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Abstract

Opioid use disorder (OUD) has become a leading cause of death in the US, yet current therapeutic strategies remain highly inadequate. To identify novel 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 did not interfere with the antinociceptive effect of opioids in rat models of neuropathic pain. 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. Our 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 option for this disorder.

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Bosse, G. D., Cadeddu, R., Floris, G., Farero, R., Vigato, E., Lee, J., Zhang, T., Gaikwad, N., Keefe, K., Phillips, P. E. M., Bortolato, M., Peterson, R. T.. 2020-09-16. The 5α-reductase inhibitor finasteride reduces opioid self-administration. https://doi.org/10.1101/2020.09.15.291609

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