OPIATE ACTIONS--NEUROPEPTIDES AND BRAINSTEM MECHANISMS

这个项目试图确定脑干电路参与 阿片类药物在吗啡耐受/依赖过程中的自主神经作用 戒烟。解决这个问题的方法是双管齐下的。第一，要 阿片肽基因表达位点的建立 大鼠延髓的原位氢化，并与 定量原位杂交，以确定吗啡如何 耐受/依赖和纳洛酮催促戒断对mRNA的影响 生产阿片剂和其他延髓神经肽。第二，到 确定延髓吻侧腹侧核、延髓腹侧核和延髓延髓前部腹侧外侧核 孤束和延髓尾侧腹侧 吗啡戒断后自主神经症状的表达 麻醉大鼠急性生理系列实验 以前对吗啡耐受/依赖：a)注意其影响 这些延髓核中的病变以及它们向其他 脑区血流动力学变化、交感神经活动和 纳洛酮治疗前后血浆加压素浓度的变化 急促戒断，b)通过确定自主神经症状是否 微量注射纳洛酮可诱发吗啡戒断 这些脑干区，C)通过记录识别的细胞(例如，在RVL中， 经鉴定为压力敏感、棘突突起的细胞) 心血管延髓核团和记录的活动变化 纳洛酮催促戒断。

This project seeks to determine the brainstem circuitry involved in the autonomic action of opiates during morphine tolerance/dependence and withdrawal. The approach to the problem is two pronged. First, to establish the sites of gene expression of the opiate peptides in the medulla of rats through the use of in situ hydridization and, with quantitative in situ hybridization, to determine how morphine tolerance/dependence and naloxone precipitated withdrawal affect mRNA production of opiate and other medullary neuropeptides. Second, to determine the role of the rostral ventral lateral medulla, nucleus of the solitary tract and the caudal ventral lateral medulla in the expression of the autonomic symptoms of morphine withdrawal through a series of acute physiological experiments in anesthetized rats previously made tolerant/dependent to morphine: a) by noting the effect of lesions in these medullary nuclei and in their projections to other brain areas on hemodynamic changes, sympathetic nerve activity and plasma vasopressin concentration during and following naloxone precipitated withdrawal, b) by determining if the autonomic symptoms of morphine withdrawal can be elicited by microinjections of naloxone into these brainstem areas, C) by recording identified cells (e.g. in RVL, cells identified as barosensitive, spinally projecting) in these cardiovascular medullary nuclei and noted activity changes during and following naloxone precipitated withdrawal.