# Exploring steroid-based therapies to reduce opioid abuse

> **NIH NIH R21** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $190,625

## Abstract

PROJECT SUMMARY
Opioid misuse and dependence have become one of the largest public health crises in the US, with devastating
socio-economic repercussions. In the attempt to curb this epidemic, NIH has recently issued the HEAL initiative
to promote the development of novel and better strategies for OUD prevention and therapy. The goal of our team
is to develop novel non-opioid drugs that may prevent or counter the abuse liability of opioids. To this end, the
Peterson lab has recently developed a high-throughput zebrafish assay to screen for drugs that may reduce
opioid self-administration. Drug screening with this paradigm revealed that one of the most effective molecules
to suppress opioid seeking was finasteride (FIN), a drug approved for clinical use with good safety and
tolerability. FIN inhibits 5α-reductase (5αR), the enzyme catalyzing the rate-limiting step in the synthesis of
several neurosteroids (including allopregnanolone and other allosteric modulators of GABA-A receptors), as well
as in the metabolism of testosterone and corticosterone. However, the specific changes in steroid profiles
whereby FIN reduces opioid self-administration remain unclear. Over the past few years, the Bortolato group
has studied the behavioral effects of FIN in rodent models of psychiatric disorders and found that this drug
reduces the severity of impulsive behaviors and self-administration of other drugs of abuse. These studies have
also shown that FIN’s effects are related to dopamine signaling, but do not affect the function of opioid receptors.
Accordingly, our preliminary data show that FIN does not interfere with the analgesic properties of opioids in rat
models. The exploratory collaborative studies proposed in this application are aimed at obtaining critical
data on the translational power of our discoveries on the zebrafish model and ascertain the mechanisms
whereby FIN reduces opioid self-administration. The two aims of this proposal will: 1) use a well-validated
rat model to test whether opioid self-administration is reversed or prevented by FIN, and study potential sex
differences in relation to these effects; and 2) use the high-throughput zebrafish model to identify which steroids
(substrates and products of 5αR) are responsible for the effects of FIN on opioid self-administration. The results
of the proposed studies will lead to future studies to validate the effects of FIN on multiple stages of opioid self-
administration (also in rat models of chronic and neuropathic pain) and the steroid-based mechanisms whereby
FIN modifies the rewarding effects of opioids. Given that FIN has been used in patients for more than 25 years
and has a very good tolerability and safety profile, these studies may rapidly lead to clinical trials on its use
as an adjunct treatment to opioid pain-killers that may reduce opioid abuse liability without interfering with the
analgesic properties of these drugs.

## Key facts

- **NIH application ID:** 10140323
- **Project number:** 5R21DA049530-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Marco Bortolato
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $190,625
- **Award type:** 5
- **Project period:** 2020-04-15 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10140323

## Citation

> US National Institutes of Health, RePORTER application 10140323, Exploring steroid-based therapies to reduce opioid abuse (5R21DA049530-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10140323. Licensed CC0.

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