COCAINE ABUSE--SYMPATHETIC & CARDIOVASCULAR CONSEQUENCES

在过去的几年里，可卡因的使用大大增加了 以及美国与可卡因相关的死亡率。临床和 病理报告表明，许多毒性与 可卡因的使用是由于这种药物对心血管的作用所致 系统。黄连对心血管影响的机制(S) 可卡因在很大程度上仍不为人所知。然而，人们普遍认为，许多人 这些反应中的一种是由可卡因介导的中枢神经系统 感同身受的流出。这一信念最近受到了研究的挑战 在麻醉和去大脑的制剂中，表明可卡因可能 实际上抑制了中枢性交感神经流出。因此，总的目标是 这一应用的特点是表征可卡因对人的影响 清醒和麻醉大鼠的中枢交感神经系统， 特别注意脑干部位和机制 牵涉其中。在这些研究中将使用三种主要策略。第一 研究将表征动脉压、心率的频谱 和可卡因在清醒和清醒状态下引起的交感神经反应 麻醉大鼠。第二，特定的单胺类拮抗剂将 微量注射入延髓吻侧腹外侧区(RVLM) 延髓腹内侧核和中缝尾侧核阻断 可卡因引起的交感神经和心血管反应。 第三，将使用电生理单一单位记录技术 识别和描述RVLM、RVMM和 中缝核团与交感神经放电和/或 心脏周期。静脉注射可卡因对大鼠脑电活动的影响 这些交感神经元的放电将被测试。离子导入法 在这些神经元上应用特定的拮抗剂将被用来 确定作用机制(S)(单胺类和/或局麻药) 对可卡因对这些神经元的影响负责。成功 这些研究的完成将提供新的重要信息 关于参与调解的中心地点和机制 可卡因对老年人交感神经和心血管系统的影响 清醒和麻醉的大鼠。这些研究还将提供第一个 RVMM和中缝尾侧交感神经元的特征 原子核。最后，将开发一个新的、有用的模型来研究 拟交感神经制剂的交感神经和心血管作用 清醒和麻醉大鼠的苯丙胺。

The last several years has seen a profound increase in the use of cocaine and cocaine-related mortality in the Unites States. Clinical and pathological reports indicate that much of the toxicity associated with cocaine use results from the actions of this drug on the cardiovascular system. The mechanism(s) responsible for the cardiovascular effects of cocaine remain largely unknown. However, it is widely accepted that many of these responses result from a cocaine-mediated increase in central sympathetic outflow. This belief has recently been challenged by studies in anesthetized and decerebrate preparations which show that cocaine may actually inhibit central sympathetic outflow. Therefore, the overall goal of this application is to characterize the effects of cocaine on the central sympathetic nervous system in conscious and anesthetized rats, with special attention being paid to the brain stem sites and mechanisms involved. Three main strategies will be used in these studies. The first studies will characterize the spectrum of arterial pressure, heart rate and sympathetic nerve responses elicited by cocaine in conscious and anesthetized rats. Second, specific monoaminergic antagonists will be microinjected into the rostral ventrolateral medulla (RVLM), rostral ventromedial medulla (RVMM) and caudal raphe nuclei in an effort to block the sympathetic nerve and cardiovascular responses elicited by cocaine. Third, electrophysiological single unit recording techniques will be used to identify and characterize individual neurons in RVLM, RVMM and the raphe nuclei with activity related to sympathetic nerve discharge and/or the cardiac cycle. The effect of intravenously administered cocaine on the discharges of these sympathetic neurons will be tested. Iontophoretic application of specific antagonists onto these neurons will be used to identify the mechanism(s) (monoaminergic and/or local anesthetic) responsible for the effects of cocaine on these neurons. Successful completion of these studies will provide new and important information regarding the central sites and mechanisms involved in mediating the effects of cocaine on the sympathetic and cardiovascular systems in conscious and anesthetized rats. These studies will also provide the first characterization of sympathetic neurons in RVMM and the caudal raphe nuclei. Finally, a new and useful model will be developed to study the sympathetic and cardiovascular effects of sympathomimetic agent such as amphetamine in conscious and anesthetized rats.