Estradiol replacement in ovariectomized female rats enhances mephedrone‐induced disruptions of nonspatial learning

Abstract

Both ovarian hormones and mephedrone, a new substance of abuse, have been observed to affect learning and memory in rats. The interaction between mephedrone and estradiol on learning was examined by administering mephedrone to ovariectomized female rats with and without estradiol hormone replacement. To assess learning, rats were trained to respond under a multiple schedule with repeated‐acquisition and performance components. Ovariectomized rats received subcutaneous capsules containing 25% 17‐β estradiol at the start of the experiment to determine the dose‐effects of mephedrone in the presence of estradiol. These capsules were then removed to determine full dose‐response curves for mephedrone in the absence of estradiol. Acute intraperitoneal injections of mephedrone (1 – 10 mg/kg) were administered twice per week. In both the presence and absence of estradiol, mephedrone produced dose‐dependent rate‐decreasing and error‐increasing effects in the acquisition and performance components in all subjects; however, the higher doses of mephedrone produced greater error‐increasing effects when estradiol was present. Three out of the 5 rats were also more sensitive to the dose‐dependent rate‐decreasing effects of mephedrone in both components when estradiol was present. These data indicate that estradiol can enhance the disruptive effects of mephedrone on learning in female rats.