PROJECT SUMMARY We propose to develop and optimize an advanced neurochemical recording technique that would be able to measure relatively rapid physiologically representative second-to-second changes in basal concentrations of specific neurochemicals, such as dopamine, in the brains of awake behaving animals. Microdialysis, a commonly used in vivo sampling technique, is able to measure changes that occur in basal levels. However, in practice the sampling timescale is significantly limited to minute-to-minute changes and it suffers from poor spatial resolution and induces significant tissue damage. As well, conventional in vivo electrochemical recording techniques, such as fast-scan cyclic voltammetry, are intrinsically limited to measuring phasic (stimulation-induced) changes in neurochemical concentrations and not changes in basal concentrations. The proposed electrochemical technique we call Multiple Cyclic Square Wave Voltammetry (M-CSWV) will enable second-to-second measurements of basal extracellular levels of neurochemicals with exceptional spatial resolution, sensitivity, specificity, and minimal tissue disturbance. This proposal leverages our unique expertise in neuroscience, electrochemistry, software development, and engineering to develop and validate this novel neurochemical recording technology for broad use in basic neuroscience research, clinical brain neuromodulation, and a variety of electrochemical applications. Our initial animal studies will guide and inform the application of our investigational technique for use by the general neuroscience and medical community. Our proposal seeks to (1) establish M-CSWV as a reliable research tool that is capable of identifying and quantifying basal dopamine extracellular levels in vivo with unsurpassed sensitivity and selectivity; and (2) validate the use of M-CSWV for in vivo chronic selective measurement of basal dopamine concentrations and application in an animal model of drug-induced neurochemical sensitization.