Effects of insulin on the mesoaccumbens dopamine system

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DESCRIPTION (provided by applicant): The postingestive effects of a meal can have a substantial influence on that meal's preference value. This influence is most likely mediated by the interaction between peripheral metabolic signals and the neural mechanisms controlling feeding behavior. The current project aims to investigate the effects of peripheral insulin on the central motivational system. The proposed hypothesis is that elevated plasma insulin facilitates the release of dopamine in the nucleus accumbens of the rat. This hypothesis will be tested by using in vivo microdialysis to assess dopamine release in combination with a hyperinsulinemic-euglycemic clamping technique to accurately determine insulin's effects by controlling for insulin-induced hypoglycemia. Thus, this approach will not only allow for an examination of the concentration effects of peripheral insulin on dopamine release (Specific Aim I), but will provide a means for investigating whether insulin's modulation of food-related dopamine release affects food preference (Specific Aim II). Furthermore, the specificity of insulin's effects on dopamine release will be verified by using in vitro voltammetry in an accumbens slice preparation (Specific Aim III). Insulin's modulation of food-related dopamine release may serve to increase the positive effects of palatable foods to contribute to pathological overeating and diet-induced obesity.