Tallia Pearson, Sarah B. Ethridge, Madison Marcus, Huailin Zhang, 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 purpose of the present study was to determine the role of these hormones in proestrus-induced decreases in heroin intake through the use of the estrogen receptor antagonist, raloxifene, and the progesterone receptor antagonist, mifepristone. Normally cycling female rats were implanted with intravenous catheters and trained to self-administer heroin on a fixed ratio (FR1) schedule of reinforcement. The estrous cycle was monitored daily via vaginal lavage and cytology prior to each test session. If a rat was in proestrus, it was treated with either vehicle (peanut oil), raloxifene, mifepristone, or a combination of raloxifene and mifepristone 30 min before the session. Mifepristone failed to block proestrus-induced decreases in heroin intake when administered alone. In contrast, raloxifene significantly blocked proestrus-induced decreases in heroin intake when administered alone, and these effects were not further enhanced by co-administration of mifepristone. These data suggest that estradiol (but not progesterone) decreases heroin intake in normally cycling rats during proestrus.