Can 17-estradiol attenuate corticosterone-induced depressive-like behavior in middle-aged gonadectomized male and female rats?

Major affective disorder (MDD) is a subtype of depression that affects over 280 million people worldwide with stress being important risk factors. Women are twice as likely to develop MDD than men, especially within middle-age when estrogen levels fluctuate and then wane. Our study used a preclinical depressive-like model, using 40mg/kg of CORT which was injected subcutaneously daily over 4 weeks to determine whether depressive-like behavior would be attenuated with estradiol treatment (0.3ug) in both male and female gonadectomized, middle-aged rats. My honor’s thesis will focus on the sucrose preference (SP) and radial arm water maze (RAWM) tasks, two key tasks that can assess anhedonia and spatial working memory. For our modified SP, the task involves a two-bottle choice (water and sucrose) and exposed the rats to the two bottles for ten days with assessment performed on the last three days after acclimation. For RAWM, rats are placed into a symmetrical maze with eight arms connected to a circular center and filled with water. Rats must find four platforms located within four different arms throughout 4 trials. When a platform is located, the platform is removed and so rats must remember which platform was found and avoid that arm and then find one of the three remaining platforms. This causes working memory load to increase with trials. Four trials are given each day for twelve days. The results showed that CORT impaired early-phase RAWM performance in females, while E2 improved performance across all phases. In males, CORT unexpectedly improved early performance, and E2 caused early impairments followed by mid-phase improvements. However, the results seen in the early phase for males should be taken with caution as we had to use the average of their respective treatment group for data interpretation since their sessions were terminated early. SP outcomes showed no effects of CORT or E2 on sucrose preference, although females exhibited higher preference overall and E2 increased fluid consumption. We interpret these results to show that E2 can enhance spatial working memory within females and males with more robust effects in females. The early-phase CORT-induced impairment in females aligns with prior findings that stress hormones can disrupt hippocampal function and spatial learning. The lack of impact on sucrose preference suggests that neither hormone robustly influenced depressive-like behavior within our model.