COCAINE ABUSE--SYMPATHETIC & CARDIOVASCULAR CONSEQUENCES

可卡因滥用——同情

• 批准号: 2120737
• 负责人: Kurt J. Varner
• 金额: $ 12.3万
• 依托单位: LSU HEALTH SCIENCES CENTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-02-15 至 1997-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2120737
• 关键词: amines; blood pressure; brain stem; cardiovascular function; cardiovascular pharmacology; cocaine; dorsal raphe nucleus; drug abuse; drug addiction antagonist; electrophysiology; heart rate; laboratory rat; microinjections; neuropharmacology; nontherapeutic iontophoresis; stimulant /agonist; sympathetic block; sympathetic nervous system

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.

最近几年，可卡因的使用大幅增加 和可卡因相关的死亡率。临床和 病理报告表明，与 可卡因使用该药物对心血管的作用结果 系统。负责心血管影响的机制 可卡因在很大程度上未知。但是，很多人都广泛接受 这些响应是由可卡因介导的中央介导的增加而产生的 同情流出。该信念最近受到研究的挑战 在麻醉和杂交的准备工作中，表明可卡因可能 实际上抑制了中心同情流出。因此，总体目标 该应用的表征可卡因对 有意识和麻醉大鼠的中心同情神经系统， 特别注意脑干位点和机制 涉及。这些研究将使用三种主要策略。第一个 研究将表征动脉压，心率的光谱 可卡因在有意识和 麻醉大鼠。第二，特定的单胺能拮抗剂将是 显微注射到鼻腹侧外侧髓质（RVLM），thostral 腹侧髓质（RVMM）和尾raphe核，以阻止 可卡因引起的交感神经和心血管反应。 第三，将使用电生理单位记录技术 识别和表征RVLM，RVMM和 raphe核具有与交感神经排出和/或 心脏周期。可卡因对可卡因的影响 这些交感神经元的排出将测试。离子遗迹 将特定拮抗剂应用于这些神经元将用于 确定机制（单胺能和/或局部麻醉） 负责可卡因对这些神经元的影响。成功的 这些研究的完成将提供新的重要信息 关于介导的中央站点和机制 可卡因对交感神经和心血管系统的影响 有意识和麻醉的大鼠。这些研究还将提供第一个 RVMM和尾raphe中交感神经元的表征 核。最后，将开发一种新的有用模型来研究 交感神经的交感神经和心血管效应，例如 有意识和麻醉大鼠的苯丙胺。