# The Influence of Gonadal Hormones on Opioid Use

> **NIH NIH R01** · DAVIDSON COLLEGE · 2020 · $321,886

## Abstract

PROJECT SUMMARY
Preclinical, clinical, and epidemiological studies have consistently revealed sex- and gender-related
differences in substance use and the development of substance use disorders. Many of these sex
differences can be attributed to gonadal hormones, and the effects of ovarian hormones across the
estrous/menstrual cycle have been well documented for cocaine, methamphetamine, and other
stimulants. Far fewer studies have examined the role of androgen hormones on drug sensitivity, and
relatively few studies have examined the role of ovarian hormones on the self-administration of heroin
and other opioids. This represents a limitation of the existing literature, given evidence that gonadal
hormones alter sensitivity to the abuse-related effects of opioids in a manner very differently from the
way they alter sensitivity to the effects of stimulants. The scientific objective of the proposed project is to
characterize the effects of ovarian and androgen hormones on heroin self-administration in sexually
mature male and female rats, while identifying hormonally based treatment interventions for opioid use
disorders. To this end, Aim 1 will examine the effects of exogenous estradiol, progesterone, and their
combination on heroin self-administration in gonadectomized male and female rats. Aim 2 will examine
the role of endogenous ovarian hormones in the suppression of heroin self-administration during
proestrus through receptor-selective antagonists. Aim 3 will examine the effects of exogenous estradiol
and progesterone on heroin self-administration in gonadally intact female rats. Aim 4 will examine the
effects of exogenous testosterone on heroin self-administration in gonadectomized male and female rats.
Finally, Aim 5 will examine the effects of an androgen steroid inhibitor on heroin self-administration in
gonadally intact male rats. The ultimate goal of these studies is to better predict sex-related differences
in opioid use disorders and to identify novel and sex-specific treatment interventions for opioid abuse and
addiction.

## Key facts

- **NIH application ID:** 9983625
- **Project number:** 5R01DA045364-03
- **Recipient organization:** DAVIDSON COLLEGE
- **Principal Investigator:** Mark A Smith
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $321,886
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9983625

## Citation

> US National Institutes of Health, RePORTER application 9983625, The Influence of Gonadal Hormones on Opioid Use (5R01DA045364-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9983625. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*