Project Summary Individuals decide between alternatives based on their perceived value of the reward associated with each option. In humans, this value-based decision-making behavior varies by sex and across the menstrual cycle. However, it is not understood how endogenous sex hormones influence the neural dynamics that underlie decision-making. 17b-estradiol, the principle estrogenic hormone that varies in expression across the menstrual cycle, is a compelling candidate because it is known to activate dopaminergic signaling in the nucleus accumbens, a key center for reward processing in the brain. This work will address two questions: 1) What is the effect of 17b-estradiol on rats’ value-based decision-making? 2) What is the in vivo mechanism by which 17b-estradiol modulates dopaminergic signaling during value-based decision-making behavior? This project will address these questions with state-of-the-art tools, including fiber photometry imaging, mass spectrometry, and cutting-edge computational methods. It will characterize the interactions between 17b-estradiol and dopamine signaling in rats performing a novel value-based decision-making behavior in naturally cycling females, in ovariectomized females with and without an exogenous dose of 17b-estradiol, and in males. This proposal will establish how 17b-estradiol affects the behavioral engagement of the dopaminergic system and the dynamics of downstream circuits in rats performing a rich, quantifiable value-based decision-making behavior.