A Novel Drug with Potentially Tissue-Specific Estradiol-like Actions Enhances Spatial Reference Memory in Young Ovariectomized Rats
Sundin, Britny; Talboum, Joshua; Prokai, Kati; Prokai, Laszlo; and Bimonte-Nelson, Heather
Department of Psychology, Behavioral Neuroscience, Arizona State University
As women age, menopause ensues and ovarian hormones, including estrogen, drastically decrease. Estrogen replacement in menopausal women and in the ovariectomized (Ovx) rodent model has been linked to positive effects on memory, as well as protective neurobiological effects in cognitive brain areas. Yet, despite the positive effects, there are risks associated with hormone replacement, such as endometrial cancer. This leaves the problem of finding a hormone therapy that retains the cognitive benefits while obviating the negative effects. Recently, a new estrogen-related drug (Drug Q) was developed that, in the rat, has been shown to act only in the brain and not on the uterus. The current study tested this new drug to determine whether it retains the memory enhancing effects of estrogen. Young Ovx rats were divided into 4 groups of 8 subjects: one group was injected with 10 micrograms of Drug Q, one with 50 micrograms of Drug Q, one with 10 micrograms of estradiol, and one with vehicle (sesame oil) as a control. Cognitive performance was evaluated using the spatial reference memory Morris water maze. We found that Drug Q enhanced performance to that of estradiol. Indeed, Ovx rats given estradiol or either dose of Drug Q swam a lesser distance to the platform on the last trial on the first day of testing. These data suggest that estradiol and both doses of Drug Q improved the ability to navigate through and learn a new environment on the first day of testing.