Immune, Hormonal and Neural Mechanisms of Feeding Behavior

进食行为的免疫、激素和神经机制

• 批准号: RGPIN-2014-05094
• 负责人: Ossenkopp, KlausPeter
• 金额: $ 2.48万
• 依托单位: University of Western Ontario
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=588207
• 关键词: Immune; Hormonal; Neural; Mechanisms; Feeding

All organisms need to solve the problem of obtaining proteins, carbohydrates, fats and other nutrients from their environment without absorbing significant amounts of toxins, as many plants (and animals) produce toxins to protect against herbivory (or predation). Mammals have evolved a number of mechanisms, both physiological and behavioral, that act as defences against the ingestion and absorption of toxins in food or water. In addition to orosensory assessment of food, postingestional effects provide important information about the nutritional and toxic characteristics of the ingested food. We have characterized the effects of high doses of the toxin LiCl on learning mechanisms involved in the toxin defence system and low doses of this toxin, presented in food, on feeding behaviors. We have shown that large doses of the toxin will not only condition strong disgust responses (gaping) in rats when a novel taste is paired with the effects of the toxin, but a novel context also acquires the ability to elicit disgust responses when paired with the toxin. Of interest to us are the neural systems that are mediating the conditioning of disgust reactions to a context and we will use a lesion approach to examine the roles of the vagus nerve, the brainstem chemosensor (area postrema) and the gustatory insular cortex. We have also demonstrated that rats made sick by activating their immune system with a bacterial mimetic, will not show this type of conditioned disgust, either to a taste cue or a context. Of interest here is to determine how activation of the immune system blocks memory formation. When small doses of LiCl are mixed into a food rats will reduce their food intake to keep the toxin level below a certain threshold value, indicating that the rats are able to track ingested toxin levels. We will again be examining the roles of the same neural structures (vagus, area postrema, insular cortex) in this important phenomenon by using a lesion approach. The role of immune system stimulation in this process will also be examined as will putative age (adolescence and adult) and sex differences in this toxin tracking phenomenon. The overall thrust of this project is to characterise the negative side of incentive motivation (nausea and disgust) related to the toxin defence system.

所有生物体都需要解决从环境中获取蛋白质、碳水化合物、脂肪和其他营养物质而不吸收大量毒素的问题，因为许多植物（和动物）会产生毒素来防止食草（或捕食）。哺乳动物已经进化出了许多生理和行为机制，可以防御食物或水中毒素的摄入和吸收。除了食物的口腔感觉评估之外，食后效应还提供有关摄入食物的营养和毒性特征的重要信息。我们已经描述了高剂量的 LiCl 毒素对毒素防御系统中涉及的学习机制的影响，以及食物中存在的低剂量的这种毒素对进食行为的影响。我们已经证明，当新的味道与毒素的作用相结合时，大剂量的毒素不仅会引起大鼠强烈的厌恶反应（目瞪口呆），而且当新的环境与毒素相结合时，也会获得引起厌恶反应的能力。我们感兴趣的是调节对环境的厌恶反应的神经系统，我们将使用损伤方法来检查迷走神经、脑干化学传感器（后区）和味觉岛叶皮层的作用。我们还证明，通过用细菌模拟物激活免疫系统而生病的老鼠，不会表现出这种条件性厌恶，无论是对味觉提示还是环境。这里感兴趣的是确定免疫系统的激活如何阻止记忆形成。当小剂量的氯化锂混合到食物中时，老鼠会减少食物摄入量，以将毒素水平保持在某个阈值以下，这表明老鼠能够追踪摄入的毒素水平。我们将通过使用损伤方法再次检查相同神经结构（迷走神经、后区、岛叶皮层）在这一重要现象中的作用。免疫系统刺激在此过程中的作用也将受到检查，这种毒素追踪现象中的假定年龄（青春期和成人）和性别差异也将受到检查。该项目的总体主旨是描述与毒素防御系统相关的激励动机（恶心和厌恶）的消极一面。