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.

Public Health Relevance

Opioid addiction has reached epidemic levels in many parts of the United States and throughout the world. Furthermore, there are important sex- and gender-related differences in the rates, patterns, and trajectories of opioid abuse. This project will examine the effects of gonadal hormones (e.g., estradiol, progesterone, and testosterone) on heroin self-administration in males and females, and it will examine hormonally based treatments for reducing heroin use.

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA045364-02
Application #
9787423
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Moore, Holly Marie
Project Start
2018-09-30
Project End
2023-07-31
Budget Start
2019-08-01
Budget End
2020-07-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Davidson College
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
071059042
City
Davidson
State
NC
Country
United States
Zip Code
28035