Immune, Hormonal and Neural Mechanisms of Ingestive 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(和一些动物)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，摄入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。我们一直在通过研究与厌恶含有毒素的食物有关的学习机制来表征高剂量毒素(例如LiCl)对这些防御机制的影响。我们已经证明，大剂量的毒素不仅会使大鼠对含有毒素的食物的味道产生强烈的厌恶反应(例如，张口和摇头)，而且当与毒素配对时，新的背景也将获得引起条件厌恶反应的能力。然而，环境中的大多数食物往往含有低水平的毒素，我们通过在食物中混合低水平的LiCl来模拟这一过程，并检查食物摄入量和行为变化，以表明味道可口。我们发现，老鼠会减少食物摄入量，将毒素水平保持在一定的阈值以下，这表明老鼠能够跟踪摄入的毒素水平。我们还发现，雌性大鼠比雄性大鼠对高水平毒素表现出更强的条件性反应，我们计划更详细地研究这种性别差异，并研究雌性性腺激素雌二醇和黄体酮在对高水平毒素的味道和环境的条件性厌恶中所起的作用。我们还计划检查性别差异，以及性腺激素在调节大鼠摄取食物中低水平毒素的能力方面的作用。对毒素阈值的调节也将在怀孕大鼠身上进行检验。这项研究的总体主旨是确定毒素防御系统在进食中的作用，并确定防御机制(S)是否可能在雌性中更强，以防止不利的生殖后果。

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 plant (and some 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 foods, post ingestional effects provide important information about the nutritional and toxic characteristics of the ingested foods. We have been characterizing the effects of high doses of toxin (e.g., LiCl) on these defence mechanisms by examining learning mechanisms involved in aversion to foods which contain toxins. We have shown that large doses of toxin will not only condition strong disgust responding (e.g., gaping and head shaking) in rats to the taste of the foods containing the toxin, but that a novel context will also acquire the ability to elicit conditioned disgust responses when paired with the toxin. However, most foods in the environment tend to contain low levels of toxin and we have modeled this process by mixing low levels of LiCl into a food and examining both food intake and changes in behavior indicative of taste palatability. We have found that rats will reduce their food intake to keep the toxin level below a certain threshold value, indicating that rats are able to track ingested toxin levels. We have also found that female rats show a stronger conditioned response to high levels of toxin than males and we plan to examine this sex difference in more detail as well as examine the role of the female gonadal hormones, estradiol and progesterone, in conditioned disgust to both taste and context with high levels of toxin. We also plan to examine sex differences, and the role of gonadal hormones, in the ability of rats to regulate their intake of low levels of toxin in food. Regulation of the toxin threshold will also be examined in pregnant rats. The overall thrust of this program of research is to determine the role of the toxin defence system in feeding and to determine if the defence mechanism(s) may be stronger in females in order to prevent adverse reproductive outcomes.