Sarah B. Ethridge, Abigail N. Gibson, Huailin Zhang, Alexander T. Casimir, Kenzie M. Potter, Andrea M. Robinson, and Mark A. Smith
Faculty Sponsor: Dr. Mark Smith
We previously reported that heroin intake decreases markedly in female rats during the proestrus phase of the estrous cycle. During proestrus, levels of estradiol and progesterone rise and fall in quick succession, so it is not known whether estradiol, progesterone, or their combination is responsible for the observed decrease in heroin intake. The first purpose of this study was to examine the effects of chronic administration of estradiol, progesterone, and their combination in ovariectomized female rats (Experiment 1). The second purpose of this study was to determine whether chronic administration of an ovarian hormone could serve as a potential pharmacotherapy to reduce heroin intake in intact female rats (Experiment 2). In both experiments, rats were surgically implanted with intravenous catheters, trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement, and chronically administered ovarian hormones. In Experiment 1, chronic estradiol significantly decreased heroin intake relative to chronic progesterone in ovariectomized rats. In Experiment 2, chronic estradiol numerically decreased heroin intake and significantly decreased intake of the synthetic opioid remifentanil in intact female rats. Collectively, these data suggest that estradiol mediates proestrus-induced decreases in heroin intake and that estrogen-based pharmacotherapies may decreases opioid intake in females with opioid use disorder.
aculty Sponsor: Dr. Mark SmithWe previously reported that heroin intake decreases markedly in female rats during the proestrus phase of the estrous cycle. During proestrus, levels of estradiol and progesterone rise and fall in quick succession, so it is not known whether estradiol, progesterone, or their combination is responsible for the observed decrease in heroin intake. The first purpose of this study was to examine the effects of chronic administration of estradiol, progesterone, and their combination in ovariectomized female rats (Experiment 1). The second purpose of this study was to determine whether chronic administration of an ovarian hormone could serve as a potential pharmacotherapy to reduce heroin intake in intact female rats (Experiment 2). In both experiments, rats were surgically implanted with intravenous catheters, trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement, and chronically administered ovarian hormones. In Experiment 1, chronic estradiol significantly decreased heroin intake relative to chronic progesterone in ovariectomized rats. In Experiment 2, chronic estradiol numerically decreased heroin intake and significantly decreased intake of the synthetic opioid remifentanil in intact female rats. Collectively, these data suggest that estradiol mediates proestrus-induced decreases in heroin intake and that estrogen-based pharmacotherapies may decreases opioid intake in females with opioid use disorder.
