Estradiol (E2) is the most potent and prevalent form of estrogen, a well-known hormone that regulates multiple tissues and func-tions in humans. In the brain, E2 regulates processes as diverse as learning, memory, cognition, mood, as well as neurodevelopment and neurodegeneration. The actions of E2 are mediated by classical estrogen receptors (ERs; α and β), and by the G protein-coupled estrogen receptor 1 (GPER or GPR30) (Prossnitz and Arterburn, 2015). Classical ER are predominantly present in the nucleus and cytoplasm, with less than 2% present on the plasma membrane, and mediate genomic cellular effects that occur in the time frame of hours to days (Prossnitz and Arterburn, 2015). GPER is expressed on the plasma membrane, and on intracellular membranes of the endoplasmic reticulum and Golgi apparatus, and mediates rapid estrogen-induced effects that occur in the time frame of seconds to minutes (Prossnitz and Arterburn, 2015).