The Effect of Flutamide on Spatial Working Memory and Serum Estrogen Levels in Female Rats

Abstract

In the absence of testosterone, the brain, by default, differentiates into a female brain. Sex differentiation of the rat brain occurs during the perinatal period (four days prior to and four days after birth) during which time both estrogen and androgen receptors are expressed in the female brain. However, the role of androgen receptors in the differentiation of the female brain during the perinatal period is unknown. Our purpose of this study was to examine the effects of blockade of androgen receptors on circulating estrogen levels and spatial working memory. Four timed‐pregnant Long Evans rats were divided into two groups: one group (N=2) received flutamide during perinatal period whereas the other group (N=2) served as control receiving vehicle (95% Olive oil‐5% ethanol). Female pups from the flutamide group (N=8) continued to receive flutamide whereas the pups from the control group received vehicle for the additional four days (N=15). Prior to performing Radial Arm Maze test to assess their spatial working memory, adult animals were placed on a 60 % food restriction to bring their body weights close to 85% of their original weight. spatial working memory testing involved a three‐day habituation, three‐day training, and one testing day. During the habituation period, all eight arms of the Radial Arm Maze contained food. During the training and the testing periods, however, four of the eight arms contained food and the other four did not. Any‐maze software linked to a video‐tracking device tracked the amount of time each animal spent in the arms with or without food. Flutamide‐treated animals spent more time in the arms with food compared to the control group suggesting greater choice accuracy or modestly improved spatial working memory (p= 0.06). At the end of the behavioral study, animals were sacrificed and trunk blood was collected to measure serum estrogen levels using ELISA. Flutamide‐treated animals showed an increase in serum estrogen levels (p<0.05) implying a relationship between improved spatial working memory and increased levels of estrogen. Thus, this study suggests that the blockade of androgen receptors during perinatal period increases serum estrogen levels and marginally improves spatial working memory in female rats.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.