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This project proposes a multidisciplinary approach to studying vulnerability to nicotine addiction, by developing a new method using caged drugs and upconversion nanoparticles to deliver nicotine to targeted brain regions in a non-invasive and timely fashion in the behaving mouse. So far, the use of caged drugs in animals has been inadequate, as these photo-chemicals are activated by ultraviolet or visible light, which penetrates poorly into biological tissue. To overcome this problem, I propose using “upconversion nanoparticles”—nanoscale inorganic particles that have the unique property of converting near-infrared light (which can deeply penetrate biological tissue) into visible light. Nanoparticles will be injected into precise brain regions and serve as light antennas, collecting near-infrared light and transforming it into visible light, thereby releasing the systemically injected caged drug in that precise region only. My goal is threefold over three years: 1) Characterize the performance of upconversion nanoparticles and caged drugs in mice, 2) Test the transcranial photo-release of caged nicotinic agonists delivered subcutaneously, and 3) use this novel photopharmacology approach to address long-standing biological questions about nicotine addiction in mice interacting in groups. Moreover, this novel technique may be applied to further our molecular understanding of other types of brain function, as well as in the development of therapeutics with reduced side effects.