Abigail N. Gibson, Sarah B. Ethridge
Faculty Sponsor: 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, with estradiol reaching peak concentrations 8-24 hours prior to progesterone. The decreases in heroin intake reported during proestrus are believed to occur when estradiol levels are decreasing from their peak and progesterone levels are just beginning to rise; however, it is not known which of these hormones (or their combination) are responsible for decreases in heroin intake. The purpose of the present study was to model the hormonal changes that occur during proestrus in ovariectomized female rats to determine how fluctuating concentrations of estradiol and progesterone alter heroin intake. To this end, 9 female rats were ovariectomized, implanted with intravenous catheters, and trained to self-administer heroin during daily test sessions. Once responding stabilized, rats were tested at 7-day intervals under four hormonal conditions: (1) vehicle (22-hr pretreatment) + vehicle (30-min pretreatment), (2) estradiol (22-hr pretreatment) + progesterone (30-min pretreatment), (3) estradiol (22-hr pretreatment) + vehicle (30-min pretreatment), and (4) vehicle (22-hr pretreatment) + progesterone (30-min pretreatment). Estradiol + progesterone significantly decreased heroin intake relative to vehicle + vehicle, mimicking the decreases in heroin intake reported in female rats during proestrus. Interestingly, decreases in heroin intake were also observed following estradiol + vehicle but not following vehicle + progesterone. Collectively, these data suggest that high but falling levels of estradiol mediate proestrus-induced decreases in heroin intake in female rats.