Effects of insulin on the mesoaccumbens dopamine system

描述（由申请人提供）：一顿饭的进食后效应会对该餐的偏好值产生实质性影响。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。目前的项目旨在研究外周胰岛素对中枢动机系统的影响。提出的假设是血浆胰岛素升高促进了大鼠伏隔核中多巴胺的释放。这一假设将通过体内微透析来评估多巴胺释放，并结合高胰岛素-正血糖夹紧技术来准确确定胰岛素的作用，通过控制胰岛素诱导的低血糖来验证。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（Specific Aim I），还可以为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提供一种手段（Specific Aim II）。此外，胰岛素对多巴胺释放影响的特异性将通过在伏隔核薄片制备中使用体外伏安法来验证（Specific Aim III）。胰岛素对食物相关多巴胺释放的调节可能有助于增加美味食物的积极作用，从而导致病理性暴饮暴食和饮食引起的肥胖。

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.