Role of ERβ in Motivational Anhedonia

Letters & Science (College of) / Psychological & Brain Sciences

Project Description

The objective of this project is twofold: (1) to determine the role of gonadal hormones in the development of motivational anhedonia, and (2) to assess whether selective activation of estrogen receptor-β (ERβ) can reverse or prevent stress-induced deficits in motivation. To accomplish this, mice will be trained on a progressive ratio (PR) schedule of reinforcement, a well-validated measure of motivational drive. Baseline PR performance will be recorded prior to any intervention. Once stable responding is established, both male and female mice will undergo gonadectomy, and after a 10-day recovery period, allowing gonadal hormones to be eliminated, PR responding will be reassessed to determine hormone-dependent changes in motivation. Next, mice will be divided into stressed and non-stressed groups. Within each condition, animals will receive either DPN (a selective ERβ agonist) or vehicle 30 minutes before an acute footshock stress session. PR responding will then be evaluated to measure the impact of ERβ activation on acute stress-induced motivational deficits. After responding stabilizes again, mice will be re-exposed to the stress environment for 10 minutes without shock and retested on PR to determine whether prior DPN administration has prophylactic efficacy in preventing motivational anhedonia.

Tasks and Responsibilites

Student Tasks: The student will play an active role in all stages of the project, gaining hands-on experience in behavioral neuroscience, surgery, and data analysis. Their primary responsibility will be to train mice on the progressive ratio (PR) schedule of reinforcement, including daily behavioral sessions, monitoring performance, and ensuring stable responding before experimental manipulations. The student will also be trained to perform gonadectomy surgeries on both male and female mice, followed by administering postoperative care and closely monitoring animals to ensure recovery and overall health. In addition, the student will conduct all stress-related procedures and drug administrations, including preparing and administering the ERβ agonist DPN or vehicle prior to acute footshock stress. They will run all PR testing sessions following stress or treatment conditions and maintain accurate, well-organized behavioral records. Beyond the experimental work, the student will be responsible for data collection, statistical analysis, and generating behavioral plots, calculating motivational indices, and identifying trends in performance across conditions. Finally, the student will contribute to interpreting the results, discussing findings in the context of hormone-dependent motivation and ERβ signaling. These responsibilities will provide comprehensive training across behavioral, surgical, and analytical domains.