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

Abstract

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. 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. 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 1.75mg, sc), estradiol (0.0005 or 0.005mg, sc), progesterone, (0.0125 or 0.125mg, sc), or their vehicles. After 14days of chronic treatment, a dose-effect curve was determined for heroin (0.0003-0.03mg/kg/infusion) over the course of one week. Neither testosterone nor estradiol altered responding maintained by heroin. In contrast, the high dose of progesterone (0.125mg) 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. 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.