PUBLICATION
The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder
- Authors
- Bosse, G.D., Cadeddu, R., Floris, G., Farero, R.D., Vigato, E., Lee, S.J., Zhang, T., Gaikwad, N.W., Keefe, K.A., Phillips, P.E., Bortolato, M., Peterson, R.T.
- ID
- ZDB-PUB-210414-5
- Date
- 2021
- Source
- The Journal of Clinical Investigation 131(10): (Journal)
- Registered Authors
- Bosse, Gabriel, Peterson, Randall
- Keywords
- Addiction, Drug screens, Neuroscience
- MeSH Terms
-
- 5-alpha Reductase Inhibitors/pharmacology*
- Animals
- Disease Models, Animal
- Finasteride/pharmacology*
- Humans
- Male
- Opioid-Related Disorders/drug therapy*
- Opioid-Related Disorders/physiopathology
- Rats
- Rats, Sprague-Dawley
- Zebrafish
- PubMed
- 33848264 Full text @ Journal of Clin. Invest.
Citation
Bosse, G.D., Cadeddu, R., Floris, G., Farero, R.D., Vigato, E., Lee, S.J., Zhang, T., Gaikwad, N.W., Keefe, K.A., Phillips, P.E., Bortolato, M., Peterson, R.T. (2021) The 5α-reductase inhibitor finasteride reduces opioid self-administration in animal models of opioid use disorder. The Journal of Clinical Investigation. 131(10):.
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 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping