Abstract The center uses novel strategies to determine the mechanism(s) of action for the anti- depressant actions of neurosteroids. A panel of neurosteroid analogues with a range of previously determined mechanisms of action will be synthesized in the Chemistry Core for use in all Projects in the center. These include analogues with actions at NMDA receptors, GABAA receptors, Ca2+- channels, and intracellular targets. New tethered compounds will be synthesized to restrict actions to plasma-membrane channels. Existing and proposed photoaffinity labeling neurosteroids will be prepared in the core and used in Project 1 to identify novel sites. The core is a hub for evaluation of the impact of neurosteroids with varied cellular actions.