One aspect of the present disclosure includes a closed-loop therapy delivery system for regulating an endogenous level of a first neuromodulatory agent in a subject. The therapy delivery system includes a sensing component, a delivery component, and a controller. The sensing component is configured to detect an extracellular level of the first neuromodulatory agent. The delivery component is configured to deliver an amount of a second neuromodulatory agent to an intraparenchymal target site of the subject. The controller is configured to coordinate operation of the sensing component and the delivery component.