Abstract
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.
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Data Availability
Data available upon request.
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Acknowledgements
The authors thank the National Institute on Drug Abuse for supplying the study drug.
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This work was supported by the National Institutes of Health [grant numbers DA045364 and DA031725 to MAS]. The NIH had no role in study design; in the collection, analysis, and interpretation of the data; in the writing of the report; and in the decision to submit the article for publication.
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MAS developed the idea and wrote the manuscript. JLS assisted in project design and management. TP, SLB, and JDC were responsible for data collection.
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Smith, M.A., Pearson, T., Ballard, S.L. et al. The effects of gonadal hormones on heroin Self-Administration in male gonadectomized rats. Psychopharmacology 241, 171–179 (2024). https://doi.org/10.1007/s00213-023-06471-y
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DOI: https://doi.org/10.1007/s00213-023-06471-y