Effects of insulin on the mesoaccumbens dopamine system

描述（由申请人提供）：一餐的摄食后效应可能对该餐的偏好值产生重大影响。这种影响很可能是由外周代谢信号和控制摄食行为的神经机制之间的相互作用介导的。本课题旨在研究外周胰岛素对中枢动力系统的影响。提出的假设是，血浆胰岛素升高促进大鼠丘脑核中多巴胺的释放。该假设将通过使用体内微透析来评估多巴胺释放，结合高胰岛素-正常血糖钳夹技术来通过控制胰岛素诱导的低血糖来准确确定胰岛素的作用。因此，这种方法不仅可以检查外周胰岛素对多巴胺释放的浓度效应（具体目标I），而且可以提供一种方法来研究胰岛素对食物相关多巴胺释放的调节是否影响食物偏好（具体目标II）。此外，胰岛素对多巴胺释放的作用的特异性将通过使用体外伏安法在一个脑片制备（具体目标III）进行验证。胰岛素对食物相关多巴胺释放的调节可能有助于增加可口食物的积极作用，从而导致病理性暴饮暴食和饮食诱导的肥胖。

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.