Neural basis of learned food aversion and nausea

描述（由申请人提供）：某些药物会产生恶心和呕吐，可能导致食欲不振和食物摄入量减少，这会对疾病的恢复产生负面影响。使用细胞毒性化疗药物时经常观察到恶心和呕吐。人们对检测毒素的神经通路和机制知之甚少。胃肠道（GI）感觉神经纤维在呕吐的发生中起重要作用，也可能参与恶心的刺激。目前的建议将集中在确定的途径和神经化学的胃肠道迷走神经和脊髓传入纤维和脑核，被激活的毒素。为了解决这个问题，将进行实验以检查顺铂（化疗剂）和氯化锂（LiCI）（在人类中产生恶心的治疗）对内脏传入神经活动以及脑和脊髓Fos表达的影响。研究将确定：（1）属性（神经递质受体，牵张敏感性，胃和肠中的神经支配部位），（2）使用Fos表达被顺铂和LiCI治疗激活的脑干和脊髓部位，（3）涉及由顺铂和LiCI使用迷走神经和GI脊神经的损伤产生的脑Fos表达的外周神经通路，以及（4）在由顺铂和LiCI处理产生的脑Fos应答中起作用的神经递质受体。对毒素检测生理学的理解可能有助于在大量临床情况下的恶心治疗，包括癌症化疗、糖尿病胃轻瘫、神经性厌食、缺血性胃病、慢性肠梗阻、腹部恶性肿瘤和功能性消化不良。恶心的有效治疗可以大大改善慢性病患者的生活质量。

DESCRIPTION (provided by applicant): Some medications produce nausea and vomiting that may lead to loss of appetite and reduced food intake, which can negatively affect recovery from disease. Nausea and vomiting are frequently observed with use of cytotoxic chemotherapy agents. Little is known about the neural pathways and mechanism for detecting toxins. Gastrointestinal (GI) sensory nerve fibers play an important role in the initiation of vomiting, and may also be involved in the stimulation of nausea. The present proposal will focus on identifying the pathways and neurochemistry of GI vagal and spinal afferent fibers and brain nuclei that are activated by toxins. To address this issue experiments will be conducted to examine the effects of cisplatin (a chemotherapy agent) and lithium chloride (LiCI) (treatments that produce nausea in humans) on visceral afferent nerve activity and brain and spinal cord Fos expression. Studies will determine: (1) the properties (neurotransmitter receptors, stretch-sensitivity, site of innervation in the stomach and intestine) of vagal and spinal afferent fibers responsive to cisplatin and LiCI using a novel application of single-unit neurophysiology, (2) the brainstem and spinal cord sites that are activated by cisplatin and LiCI treatment using Fos expression, (3) the peripheral neural pathways involved in brain Fos expression produced by cisplatin and LiCI using lesions of the vagus and GI spinal nerves, and (4) the neurotransmitter receptors that play a role in the brain Fos response produced by cisplatin and LiCI treatment. An understanding of the physiology of toxin detection may contribute to nausea treatment in a large number of clinical situations, including cancer chemotherapy, diabetic gastroparesis, anorexia nervosa, ischemic gastropathy, chronic intestinal obstruction, abdominal malignancy, and functional dyspepsia. Effective treatment of nausea may substantially improve the quality of life for patients with chronic disease.