The effects of gonadal hormones on heroin Self-Administration in male gonadectomized rats

• Published in: Psychopharmacology Vol. 241; no. 1; pp. 171 - 179
• Main Authors: Smith, Mark A., Pearson, Tallia, Ballard, Shannon L., Camp, Jacob D., Sharp, Jessica L.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 2024; Springer Nature B.V
• Subjects: 17β-Estradiol; Animals; Biomedical and Life Sciences; Biomedicine; Dietary restrictions; Drug abuse; Drug addiction; Drug self-administration; Estradiol - pharmacology; Female; Heroin; Heroin - pharmacology; Hormones; Humans; Intravenous administration; Male; Narcotics; Neurosciences; Opioids; Original Investigation; Pharmacology/Toxicology; Progesterone; Progesterone - pharmacology; Psychiatry; Rats; Rats, Sprague-Dawley; Reinforcement Schedule; Self Administration; Testosterone; Testosterone - pharmacology; Opioid; Testosterone; Progesterone; Opioid use disorder; Estradiol
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-023-06471-y

Rationale
Previous studies have shown that gonadal hormones influence opioid self-administration in female rodents, but very few studies have examined these effects in male rodents.
Objectives
The purpose of this study was to examine the effects of chronic hormone treatment on intravenous heroin self-administration in gonadectomized male rats using both physiological and supraphysiological doses of testosterone, estradiol, or progesterone.
Methods
Gonadectomized male rats were surgically implanted with intravenous catheters and trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement. Using a between-subjects design, rats were treated daily with testosterone (0.175 or 1.75 mg, sc), estradiol (0.0005 or 0.005 mg, sc), progesterone, (0.0125 or 0.125 mg, sc), or their vehicles. After 14 days of chronic treatment, a dose–effect curve was determined for heroin (0.0003—0.03 mg/kg/infusion) over the course of one week.
Results
Neither testosterone nor estradiol altered responding maintained by heroin. In contrast, the high dose of progesterone (0.125 mg) reduced responding maintained by all doses of heroin to saline-control levels. This dose of progesterone did not reduce responding maintained by food on a progressive ratio schedule in either food-restricted or food-sated rats.
Conclusions
These data indicate that exogenous progesterone or a pharmacologically active metabolite selectively decreases heroin intake in male rodents, which may have therapeutic implications for men with opioid use disorder.