Food Reward and Stress

食物奖励和压力

基本信息

批准号：
8513323
负责人：
Yvonne Michelle Ulrich-Lai
金额：
$ 32.95万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-20 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8513323
关键词：
Address Adrenal Glands Adult Adverse effects Affect Amygdaloid structure Anxiety Attenuated Automobile Driving Behavior Behavioral Brain CREB1 gene Calories Carbohydrates Cells Cluster Analysis Confocal Microscopy Consumption Cyclic AMP-Responsive DNA-Binding Protein Development Drug Addiction Eating Emotional Energy Intake Environmental Risk Factor Fatty acid glycerol esters Food Gene Expression Genes Health Care Costs Human Hypothalamic structure Incidence Individual Intake Knowledge Lesion Medial Mediating Modeling Moods Motivation Neurons Obesity Output Pathway interactions Pattern Pharmaceutical Preparations Physiological Pituitary Gland Prefrontal Cortex Preparation Presynaptic Terminals Prevention strategy Property Public Health Rattus Recording of previous events Rewards Rodent Model Role Saccharin Self Medication Sex Behavior Signal Pathway Signal Transduction Slice Solutions Stress Sucrose Sweetening Agents Sympathetic Nervous System Synapses Synaptic plasticity Synaptophysin Testing United States Water base biological adaptation to stress combat density driving behavior drug of abuse gephyrin hypothalamic-pituitary-adrenal axis improved insight neuromechanism novel therapeutics obesity treatment pleasure postsynaptic prevent relating to nervous system response stress related disorder sugar

项目摘要

DESCRIPTION (provided by applicant): Individuals often engage in rewarding behaviors, including consuming highly-palatable, calorically- dense "comfort" foods or taking drugs of abuse, as a means of self-medication for stress relief, but the neural mechanisms underlying stress relief by palatable foods are largely unknown. We propose to study these mechanisms using a model in which rats with free access to food and water are given twice-daily access to a small amount of palatable sucrose solution or water as a control. Using this model, we have found that sucrose rats have attenuated hypothalamic-pituitary-adrenal (HPA) axis and behavioral-anxiety responses to stress and diminished stress-induced neuronal activation in brain reward regions. Moreover, the calories and other post- ingestive consequences of sucrose are neither sufficient nor necessary for the HPA dampening, suggesting that brain reward per se may mediate the response. The basolateral amygdala (BLA) is a key brain reward region that is also implicated in driving stress responses. Moreover, neural activity in the BLA is necessary for stress-dampening by sucrose, and genes related to structural and functional plasticity are up-regulated in the BLA following a history of sucrose intake. In support of this idea, immunolabeling for synaptophysin (a marker of presynaptic terminals), phosphorylated cAMP response element-binding protein (pCREB; a postsynaptic marker associated with synaptic plasticity), and gephyrin (a postsynaptic marker of inhibitory postsynaptic densities) are all increased in the BLA following sucrose. The current proposal addresses the hypothesis that palatable food dampens stress responses via pCREB-dependent synaptic remodeling in the BLA. We predict that sucrose intake increases BLA inhibitory tone, leading to attenuated stress-excitatory output. We will test this hypothesis in three specific aims. The first aim will use intra-BLA blockade of CREB/pCREB expression to determine whether this signaling pathway mediates sucrose-induced synaptic reorganization and stress- dampening. The second aim will assess structural and functional plasticity in the BLA after sucrose (using dual immunolabeling with confocal microscopy to quantify synaptic appositions onto BLA neurons, as well as whole- cell electrophysiological recordings from BLA slice preparations) to test the hypothesis that sucrose-induced synaptic remodeling results in increased inhibitory tone in BLA. The third aim will combine tract-tracing and lesion approaches to test the hypothesis that medial prefrontal cortex (mPFC) projections to BLA are necessary for sucrose-mediated synaptic remodeling and stress dampening.

描述（由申请人提供）：个人经常从事奖励行为，包括食用高度适口、热量密集的“舒适”食物或服用滥用药物，作为缓解压力的自我治疗手段，但压力背后的神经机制通过美味食物缓解症状的情况在很大程度上是未知的。我们建议使用一个模型来研究这些机制，在该模型中，可以自由获取食物和水的大鼠每天两次获取少量可口的蔗糖溶液或水作为对照。使用该模型，我们发现蔗糖大鼠减弱了下丘脑-垂体-肾上腺（HPA）轴和对压力的行为焦虑反应，并减少了大脑奖励区域中压力诱导的神经元激活。此外，蔗糖的卡路里和其他摄入后后果对于抑制 HPA 来说既不充分也不是必要的，这表明大脑奖励本身可能介导这种反应。基底外侧杏仁核（BLA）是一个关键的大脑奖励区域，也与驱动压力反应有关。此外，BLA 中的神经活动对于蔗糖缓解压力是必要的，并且在有蔗糖摄入史后，BLA 中与结构和功能可塑性相关的基因会上调。为了支持这一观点，突触素（突触前末梢的标记）、磷酸化 cAMP 反应元件结合蛋白（pCREB；与突触可塑性相关的突触后标记）和 gephyrin（抑制性突触后密度的突触后标记）的免疫标记均增加在 BLA 中仅次于蔗糖。目前的提案提出了这样的假设：美味的食物通过 BLA 中 pCREB 依赖性突触重塑来抑制应激反应。我们预测蔗糖摄入会增加 BLA 抑制张力，导致应激兴奋输出减弱。我们将在三个具体目标上检验这一假设。第一个目标是利用 BLA 内阻断 CREB/pCREB 表达来确定该信号通路是否介导蔗糖诱导的突触重组和应激抑制。第二个目标是评估蔗糖后 BLA 的结构和功能可塑性（使用共聚焦显微镜的双重免疫标记来量化 BLA 神经元上的突触并置，以及 BLA 切片制剂的全细胞电生理记录），以检验蔗糖诱导的假设突触重塑导致 BLA 抑制张力增加。第三个目标将结合束追踪和损伤方法来检验这样的假设：内侧前额皮质 (mPFC) 对 BLA 的投射对于蔗糖介导的突触重塑和压力抑制是必要的。