Effects of insulin on NAc excitatory transmission and motivation for food

胰岛素对 NAc 兴奋性传递和食物动机的影响

• 批准号: 10005346
• 负责人: Carrie Ferrario
• 金额: $ 38.65万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-05 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005346
• 关键词: AMPA Receptors; Adult; Affect; Agonist; Basal Ganglia; Behavior; Behavioral; Biochemical; Body Weight decreased; Brain; Brain region; Cardiovascular Diseases; Cells; Chronic; Cues; Data; Development; Diet; Dopamine; Dopamine D1 Receptor; Eating; Feeding behaviors; Female; Food; Foundations; Glutamates; Goals; Hippocampus (Brain); Insulin; Insulin Receptor; Letters; Literature; Malignant Neoplasms; Measures; Mediating; Motivation; Neurons; Nitric Oxide; Non obese; Non-Insulin-Dependent Diabetes Mellitus; Nucleus Accumbens; Obesity; Pharmacology; Phosphorylation; Physiological; Play; Population; Procedures; Rattus; Receptor Activation; Regulation; Reverse Transcriptase Polymerase Chain Reaction; Rewards; Role; Sex Differences; Signal Transduction; Surface; Synapses; Synaptic Transmission; System; Ventral Tegmental Area; Wood material; Work; anorexic; base; behavior test; evidence base; feeding; food craving; innovation; insight; juvenile animal; lateral ventricle; male; novel strategies; obesity prevention; patch clamp; prevent; protein expression; receptor; receptor expression; response; trafficking; transmission process

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.

摘要：胰岛素在大脑中的作用影响进食，这一点已得到充分证实。然而，很少有 了解潜在机制（综述见费尔南德斯和Torres-Aleman，2012年）。少数 研究表明，胰岛素调节大脑奖励和动机系统的功能， 寻找食物和进食行为，如神经核（NAc）。例如，激活胰岛素 受体增强NAc中多巴胺的释放，并在注入NAc时减少食物摄入 （Stouffer等人，2015; Figlewicz等人，2006）。此外，一项研究表明胰岛素可以减少兴奋性 在腹侧被盖区和一些年轻动物的研究中发现，胰岛素调节AMPA， 受体（AMPAR）突触运输（Beattie等，1995; Labouebe等，2013; Liu等， 2013年）。通过NAc中的AMPAR的兴奋性传递增加了对食物的动机（Di Ciano等人，2001）。 然而，胰岛素对NAc兴奋性传递或食物寻求的影响尚不清楚。我们的长期目标 是了解NAc兴奋性传递和觅食行为是如何被胰岛素调节的。我们 初步数据表明，胰岛素受体激活通过以下途径增加NAc的兴奋性传递： 机制涉及一氧化氮和增强谷氨酸释放，饮食诱导的肥胖减少了 胰岛素对NAc兴奋性传递的影响。此外，我们发现NAc内胰岛素增强了食物- 非肥胖大鼠的寻找行为。拟议研究的主要目标是确定 胰岛素受体激活增强NAc兴奋性传递的机制，以及胰岛素的作用 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 关于胰岛素对NAc功能的影响以及胰岛素在食物寻求中的作用的基本信息， 非肥胖和肥胖状态。