Immune, Hormonal and Neural Mechanisms of Feeding Behavior

所有生物都需要解决在不吸收大量毒素的情况下从环境中获得蛋白质、碳水化合物、脂肪和其他营养物质的问题，因为许多植物(和动物)会产生毒素来防止草食(或捕食)。哺乳动物已经进化出许多机制，包括生理和行为机制，这些机制可以防御食物或水中毒素的摄入和吸收。除了食物的感官评估外，进食后的影响还提供有关进食食物的营养和毒性特征的重要信息。我们已经表征了高剂量的氯化锂毒素对毒素防御系统所涉及的学习机制的影响，以及低剂量的这种毒素在食物中对摄食行为的影响。我们已经证明，当一种新的味道与毒素的影响相结合时，大剂量的毒素不仅会使大鼠产生强烈的厌恶反应(张口)，而且当与毒素相结合时，新的背景也会获得引起厌恶反应的能力。我们感兴趣的是调节厌恶反应的神经系统，我们将使用损毁方法来研究迷走神经、脑干化学感受器(最后区)和味觉岛叶皮质的作用。我们还证明了，通过用细菌模拟物激活免疫系统而生病的大鼠，无论是在味觉提示还是在背景下，都不会表现出这种条件厌恶。这里感兴趣的是确定免疫系统的激活如何阻止记忆的形成。当小剂量的氯化锂混合到食物中时，大鼠会减少食物的摄入量，将毒素水平保持在一定的阈值以下，这表明大鼠能够跟踪摄入的毒素水平。我们将再次使用损伤方法检查相同的神经结构(迷走神经、最后区、岛叶皮质)在这一重要现象中的作用。免疫系统刺激在这一过程中的作用也将被研究，以及假定的年龄(青春期和成年期)和性别差异在这种毒素跟踪现象中的作用。这个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)的负面特征。

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.