CHEMOSENSORY INFLUENCES OF INTRANASAL COCAINE ON THE REWARD SYSTEM - PROJECT SUMMARY CHEMOSENSORY PERCEPTION POWERFULLY INFLUENCES MOTIVATED BEHAVIORS. COCAINE, A HIGHLY ADDICTIVE PSYCHOSTIMULANT, IS PRIMARILY TAKEN INTRANASALLY (IN), A ROUTE ASSOCIATED WITH COMPULSIVE USE, TOXICITY, AND OVERDOSE RISK. IN COCAINE EVOKES A NASAL SENSORY EXPERIENCE WHICH LIKELY INFLUENCES THE EFFECTS OF THE DRUG AND POSSIBILITY OF ABUSE. I REASON THAT COCAINE-EVOKED NASAL SENSATION IS MEDIATED BY ACTIVATION OF THE TRANSIENT RECEPTOR POTENTIAL ANKYRIN 1 (TRPA1) PRESENT IN TRIGEMINAL NERVE ENDINGS IN THE NASAL CAVITY. TO MOVE TOWARDS TESTING THIS, I HELPED DEVELOP AN IN-DWELLING MICROFLUIDIC SURGICAL DEVICE, CALLED THE NASAL ACCESS PORT (NAP) WHICH PERMITS ACCESS TO THE NASAL EPITHELIUM OF FREELY-BEHAVING MICE TO ACHIEVE IN DELIVERY OF COCAINE AND OTHER DRUGS WITH PRECISE CONTROL OVER VOLUME AND THEREFORE DOSAGE. IN THIS F31, I WILL USE AN IN VIVO MULTIMODAL TOOLKIT INCLUDING THE NAP, OPTOGENETICS, ELECTROPHYSIOLOGY, FIBER PHOTOMETRY, AND PHARMACOLOGY ALL IN BEHAVING MICE TO DETERMINE THE CONTRIBUTIONS OF IN COCAINE ON BRAIN AND BEHAVIOR, AND ITS POSSIBLE MEDIATION BY NASAL SENSATION. IN AIM 1 I WILL ELUCIDATE THE EFFECTS OF COCAINE-EVOKED NASAL STIMULATION ON NEURAL ACTIVITY AND DOPAMINE DYNAMICS IN THE BRAIN'S REWARD SYSTEM. IN AIM 2 I WILL PROVIDE INSIGHTS INTO THE ROLE OF COCAINE-EVOKED NASAL STIMULATION IN GUIDING DRUG TAKING. OVERALL, THE RESULTS FROM THIS WORK WILL ENHANCE OUR UNDERSTANDING OF THE MECHANISMS OF NASAL CHEMOSENSATION AND THE EFFECTS OF INTRANASAL COCAINE ON BRAIN AND BEHAVIOR.