OPIATE ACTIONS--NEUROPEPTIDES AND BRAINSTEM MECHANISMS

该项目旨在确定脑干回路参与 阿片类药物在吗啡耐受/依赖过程中的自主作用 戒断 解决这一问题的办法是双管齐下的。 一是 建立阿片肽基因表达的位点， 大鼠的髓质，通过使用原位杂交， 定量原位杂交，以确定吗啡 耐受/依赖和纳洛酮催促戒断影响mRNA 产生鸦片和其他髓质神经肽。 二是 确定延髓头端腹外侧核的作用 延髓腹外侧区的孤束和尾侧 吗啡戒断的自主症状的表达通过一个 麻醉大鼠急性生理学系列实验 先前对吗啡产生耐受/依赖：a）通过观察 在这些髓核病变和他们的投影到其他 脑区对血流动力学变化、交感神经活动和 纳洛酮治疗前后血浆加压素浓度 突然戒断，B）通过确定是否有 吗啡戒断可以通过将纳洛酮微量注射到 这些脑干区域，C）通过记录识别的细胞（例如在RVL中， 细胞鉴定为压力敏感，脊髓突出），在这些 心血管髓核和注意到的活动变化， 纳洛酮后突然停药。

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.