Immune, Hormonal and Neural Mechanisms of Ingestive Behavior

所有生物都需要解决从环境中获取蛋白质、碳水化合物、脂肪和其他营养素而不吸收大量毒素的问题，因为许多植物（和一些动物）产生毒素以防止食草动物（或捕食）。哺乳动物已经进化出许多生理和行为机制，作为对食物或水中毒素的摄入和吸收的防御。除了对食物的口腔感觉评估外，摄入后效应还提供了有关摄入食物的营养和毒性特征的重要信息。我们一直在描述高剂量毒素的影响（例如，LiCl）对这些防御机制的研究，通过检查涉及厌恶含有毒素的食物的学习机制。我们已经证明，大剂量的毒素不仅会引起强烈的厌恶反应（例如，张着嘴和摇头），但是当与毒素配对时，一个新的环境也会获得引发条件性厌恶反应的能力。然而，环境中的大多数食物往往含有低水平的毒素，我们通过将低水平的LiCl混合到食物中并检查食物摄入量和指示味道适口性的行为变化来模拟这一过程。我们发现，大鼠会减少食物摄入量，以保持毒素水平低于一定的阈值，这表明大鼠能够跟踪摄入的毒素水平。我们还发现雌性大鼠对高水平毒素的条件反射比雄性大鼠更强，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孕酮在条件反射厌恶高水平毒素的味道和环境中的作用。我们还计划研究性别差异，以及性腺激素在大鼠调节食物中低水平毒素摄入能力方面的作用。还将在妊娠大鼠中检查毒素阈值的调节。这项研究计划的总体目标是确定毒素防御系统在喂养中的作用，并确定雌性的防御机制是否可能更强，以防止不良的生殖结果。

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.