Effects of insulin on NAc excitatory transmission and motivation for food

摘要：众所周知，胰岛素在大脑中的作用会影响进食。然而，很少有 了解潜在的机制(参见Fernandez和Torres-Aleman，2012年的回顾)。一小撮 研究表明，胰岛素调节大脑奖赏和动机系统的功能，这些系统参与了 觅食和觅食行为，如伏隔核(NAC)。例如，激活胰岛素 受体增强了NAC中的多巴胺释放，并在注入NAC时减少了食物摄入量 (Stouffer等人，2015年；Figlewicz等人，2006年)。此外，一项研究表明，胰岛素可以降低兴奋性。 在VTA中的传递和在年轻动物中的一些研究发现，胰岛素调节AMPA 皮质神经元中的受体(AMPAR)突触运输(Beattie等人，1995；Labouebe等人，2013；Liu等人， 2013)。NAC中通过AMPAR的兴奋性传递增加了对食物的动力(Di Ciano等人，2001)。 然而，胰岛素对NAC兴奋性传递或觅食的影响尚不清楚。我们的长期目标 是为了了解NAC兴奋性传递和觅食行为是如何受到胰岛素的调节的。我们的 初步数据表明，胰岛素受体的激活通过增加NAC的兴奋性传递 与一氧化氮和谷氨酸释放增加有关的机制，以及饮食诱导的肥胖降低 胰岛素对NAC兴奋性传递的影响。此外，我们发现NAC内的胰岛素可以改善食物-- 非肥胖大鼠的寻觅行为。拟议研究的主要目标是确定 胰岛素受体激活促进NAC兴奋性传递的机制及胰岛素的作用 受体激活对非肥胖和肥胖大鼠觅食行为的影响。这些研究将提供一个 胰岛素对NAC功能影响的基础知识和胰岛素在寻找食物中的作用 非肥胖和肥胖状态。

ABSTRACT: It is well-established that actions of insulin in the brain affect feeding. However, very little is known about the underlying mechanisms (see Fernandez and Torres-Aleman, 2012 for review). A handful of studies suggest that insulin modulates the function of brain reward and motivation systems that are involved in food-seeking and feeding behavior such as the nucleus accumbens (NAc). For example, activation of insulin receptors enhances dopamine release in the NAc and decreases food intake when infused into the NAc (Stouffer et al, 2015; Figlewicz et al, 2006). In addition, one study has shown that insulin reduces excitatory transmission in the VTA and a few studies in younger animals have found that insulin modulates AMPA receptor (AMPAR) synaptic trafficking in cortical neurons (Beattie et al, 1995; Labouebe et al, 2013; Liu et al, 2013). Excitatory transmission via AMPARs in the NAc increases motivation for food (Di Ciano et al, 2001). However, the effect of insulin on NAc excitatory transmission or food-seeking is unknown. Our long-term goal is to understand how NAc excitatory transmission and food-seeking behavior are modulated by insulin. Our preliminary data suggest that insulin receptor activation increases excitatory transmission in the NAc via mechanisms involving nitric oxide and enhanced glutamate release, and that diet-induced obesity reduces the effects of insulin on NAc excitatory transmission. Furthermore, we found that intra-NAc insulin enhanced food- seeking behaviors in non-obese rats. The main objectives of the proposed studies are to determine the mechanism by which insulin receptor activation enhances NAc excitatory transmission, and the effect of insulin receptor activation on food-seeking behavior in non-obese and obese rats. These studies will provide a fundamental information about the effects of insulin on NAc function and the role of insulin in food-seeking in the non-obese and obese state.