Gustatory Control of Sodium Appetite

钠食欲的味觉控制

• 批准号: 7644893
• 负责人: RALPH NORGREN
• 金额: $ 32.94万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-07-01 至 2013-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7644893
• 关键词: Amygdaloid structure; Animals; Anorexia Nervosa; Area; Avidity; Bilateral; Biological; Brain; Cell Nucleus; Contralateral; Desire for food; Dopamine; Drug Addiction; Environment; Equilibrium; Feeding behaviors; Goals; High Pressure Liquid Chromatography; Human; Hunger; Hypothalamic structure; Immunohistochemistry; Ingestion; Intake; Lateral; Lesion; Mammals; Measures; Mediating; Methods; Microdialysis; Modeling; Motivation; Neurosciences; Nucleus Accumbens; Obesity; Outcome; Pathway interactions; Pattern; Pontine structure; Process; Prosencephalon; Rattus; Research; Research Design; Rewards; Saline; Sensory; Sodium; Sodium Chloride; Stimulus; Structure of terminal stria nuclei of preoptic region; Sucrose; System; Taste Perception; Testing; Thalamic structure; Thirst; Ventral Striatum; Vision; base; depression; experience; indexing; parabrachial nucleus; pleasure; preference; prevent; relating to nervous system; research study; salt intake; sensory system; sodium ion

DESCRIPTION (provided by applicant): Reward remains a central puzzle of neuroscience. Understanding its neural bases is key in developing rationale therapies for a broad spectrum of maladies such as drug addiction, obesity, anorexia nervosa, and depression. Salt appetite is a biological drive triggered by a negative body sodium balance that offers a unique model for investigating the central mechanisms of reward. Sodium appetite fulfills all of the criteria for motivation, as do hunger and thirst, but has some distinct advantages. Its adequate stimulus is simple, the sodium ion, and in the external environment, this stimulus is transduced by a single sensory system, taste. In most mammals, including humans, recognition of sodium is innate. Under normal circumstances, animals show at best a mild preference for weak saline solutions and actively avoid strong ones. When a Na-appetite arises, however, even strong salt becomes highly preferred. The question here is how a modest shift in body sodium balance brings about a dramatic increase in the reward value of this sapid stimulus? Unlike vision, audition, and somethesis, taste has direct neural connections with the limbic forebrain, a large system that is critical to the elaboration of motivation and reward. The overall premise is that gustatory afferent activity from the second central gustatory relay, pontine parabrachial nucleus (PBN), reaches neural reward systems via these limbic connections and, during sodium need, transforms the sensory message elicited by NaCl from aversive to rewarding. We already know that lesions of the PBN prevent the expression of Na-appetite, but that damage to the thalamic and cortical gustatory areas does not. We use the release of dopamine (DA) in the nucleus accumbens as a forebrain index of reward. Sham licking sucrose produces a substantial efflux of accumbens DA even in experienced animals. Under normal circumstances, sham intake of 0.15 M NaCl produces only a small DA spike. During Na-appetite, however, salt intake releases an accumbens DA plume rivaling that of sucrose. Based on these facts, we propose three experimental challenges to the overall premise. Specifically, we will use (1) central lesions, (2) microdialysis, and (3) FOS immunohistochemistry to determine if parabrachial gustatory neural activity distributed via the limbic forebrain is necessary and sufficient for the expression of a Na-appetite, and if these same pathways are responsible for modulating the release of accumbens dopamine during the appetite. The specific limbic areas to be tested include the lateral hypothalamus, the amygdala, and the bed nucleus of the stria terminalis. Pleasure is a product of brain activity. Understanding the neural bases of pleasure or reward is key in developing rational therapies for in broad spectrum of maladies such as drug addiction, obesity, anorexia nervosa, and depression. This project investigates the neural bases of reward using the sense of taste because some gustatory stimuli are inherently rewarding or aversive. The research goal is to determine how taste neural activity reaches brain areas that produce reward and how this sensory information is transformed in the process.

描述（由申请人提供）：奖励仍然是神经科学的核心难题。了解它的神经基础是开发治疗药物成瘾、肥胖、神经性厌食症和抑郁症等广泛疾病的合理疗法的关键。盐的食欲是一种由体内负钠平衡引发的生物驱动力，它为研究奖赏的中枢机制提供了一个独特的模型。钠的食欲满足了所有的动机标准，饥饿和口渴也是如此，但有一些明显的优势。它的适当刺激是简单的，钠离子，在外部环境中，这种刺激是由一个单一的感觉系统，味觉。在大多数哺乳动物中，包括人类，对钠的识别是天生的。在正常情况下，动物最多表现出对弱盐溶液的轻微偏好，并积极避免强盐溶液。然而，当钠的胃口出现时，即使是浓盐也会变得非常受欢迎。这里的问题是，体内钠平衡的适度变化如何导致这种美味刺激的奖励价值急剧增加？与视觉、听觉和某些感觉不同，味觉与边缘前脑有直接的神经联系，边缘前脑是一个大型系统，对动机和奖励的阐述至关重要。总的前提是，味觉传入活动的第二个中央味觉中继，脑桥臂旁核（PBN），通过这些边缘连接到达神经奖励系统，在钠的需要，转换的感官信息引起的NaCl从厌恶奖励。我们已经知道，PBN的病变会阻止Na-食欲的表达，但丘脑和皮质味觉区的损伤不会。我们使用多巴胺（DA）的释放作为前脑奖励的指标。即使在有经验的动物中，假舔蔗糖也会产生大量的多巴胺外排。在正常情况下，假摄入0.15 M NaCl仅产生小的DA尖峰。然而，在钠食欲期间，盐摄入释放出与蔗糖相媲美的多巴胺羽流。基于这些事实，我们提出了三个实验挑战的整体前提。具体来说，我们将使用（1）中枢病变，（2）微透析，（3）FOS免疫组织化学来确定通过边缘前脑分布的臂旁味觉神经活动是否是表达Na-食欲所必需和充分的，以及这些相同的通路是否负责调节食欲期间多巴胺的释放。要测试的特定边缘系统区域包括外侧下丘脑、杏仁核和终纹床核。快乐是大脑活动的产物。了解快乐或奖励的神经基础是开发合理治疗药物成瘾、肥胖、神经性厌食症和抑郁症等广泛疾病的关键。本研究利用味觉来探讨奖赏的神经基础，因为某些味觉刺激本身就是奖赏或厌恶的。研究目标是确定味觉神经活动如何到达产生奖励的大脑区域，以及这种感觉信息如何在这个过程中转化。