NEUROENDOCRINE EFFECTS OF SELF ADMINISTERED COCAINE

描述：(申请人摘要) 可卡因在美国仍然是一种重要的滥用药物，除此之外 除了产生深刻的行为影响外，可卡因还会扰乱 许多物种的神经内分泌功能。对药物作用的认识 滥用神经内分泌功能具有根本性的重要性，因为它 提供有关以下情况可能发生的病理生理变化的信息 吸毒。可卡因刺激下丘脑-垂体-肾上腺(HPA)轴， 而HPA轴正常调节的中断会影响 通过改变新陈代谢来维持生理动态平衡 葡萄糖、蛋白质和脂肪。此外，免疫功能可能会受到损害。 以及对急性和慢性压力的反应和适应。 最近，暴露在压力源下以及 对HPA轴的药理学操作可以影响对和的反应 一些滥用药物的强化作用。因此，接触到 应激源和随后HPA轴的激活可能起到关键作用 在确定药物自我给药的“脆弱性”方面的作用。虽然 大量临床前研究考察了可卡因对健康的影响 神经内分泌功能已经发表，对神经内分泌功能知之甚少 可卡因自身给药对神经内分泌功能的影响 提议的实验的总体目标是利用一个实验 一种可以在大鼠体内采集血液中荷尔蒙的系统 自我给药，以获得潜在的重要可卡因 HPA轴激活与药物关系的信息 自治。拟议的研究将描述 自用可卡因与HPA激活的关系 Axis通过生成剂量响应和时间过程数据 可卡因的获取、维持、消灭和重新启动阶段 自治。假设积极的(或有反应的) 被动(应答性非应急)可卡因给药对比 对HPA轴的不同影响将通过比较受试者进行测试 在不同的应急情况下接受可卡因。建议数 研究还将产生新的信息，即先前激活的 HPA轴通过药理学和非药理学手段改变 自用可卡因对HPA轴的影响及其增强作用 可卡因的特性。这些实验的结果可能会提供新的 以及关于压力和寻求毒品之间关系的重要见解 行为。

DESCRIPTION: (Applicant's Abstract) Cocaine remains an important drug of abuse in the United States, and aside from producing profound behavioral effects, cocaine also disrupts neuroendocrine function in many species. Knowledge of the effects of drugs of abuse on neuroendocrine function is of fundamental importance because it provides information on the pathophysiological changes that can occur with drug use. Cocaine stimulates the hypothalamo-pituitary-adrenal (HPA) axis, and disruption of the normal regulation of the HPA axis can affect the maintenance of physiologic homeostasis by altering the metabolism of glucose, proteins and fats. In addition, immune function can be compromised as well as the reaction and adaptation to acute and chronic stress. Recently it has become apparent that exposure to stressors as well as pharmacological manipulation of the HPA axis can affect the responses to and the reinforcing properties of some drugs of abuse. Thus, exposure to stressors and subsequent activation of the HPA axis might play a critical role in determining "vulnerability" to drug self-administration. Although numerous preclinical studies examining the effects of cocaine on neuroendocrine function have been published, little is known about the effects of the self-administration of cocaine on neuroendocrine function. The overall goal of the proposed experiments is to utilize an experimental system where blood can be sampled for hormones in rats during the self-administration of cocaine in order to obtain potentially important information on the relationships between activation of the HPA axis and drug self-administration. The proposed studies will characterize the relationships between self-administered cocaine and activation of the HPA axis by generating dose response and time course data during the acquisition, maintenance, extinction and re-initiation phases of cocaine self-administration. The hypothesis that the active (response contingent) versus passive (response non-contingent) administration of cocaine differentially affects the HPA axis will be tested by comparing subjects that receive cocaine under different response contingencies. The proposed studies also will generate new information on whether prior activation of the HPA axis through pharmacologic and non-pharmacologic means alters the effects of self-administered cocaine on the HPA axis and the reinforcing properties of cocaine. The results of these experiments could provide new and important insights on the relationships between stress and drug seeking behavior.