ATTENUATION OF MORPHINE WITHDRAWAL BY ALPHA-INTERFERON

α-干扰素减弱吗啡戒断作用

• 批准号: 3212251
• 负责人: NICHOLAS R HALL
• 金额: $ 20.85万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1992-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3212251
• 关键词: Newcastle disease virus; analgesics; behavior test; brain mapping; catecholamines; drug addiction; drug addiction antagonist; drug tolerance; drug withdrawal; interferon inducers; interferons; laboratory rat; morphine; naloxone; neurotransmitter receptor; psychological reinforcement; psychoneuroimmunology; psychopharmacology; self medication

Interferon - a product of macrophages and B lymphocytes - has been found to exert effects at the level of the central nervous system in humans and in laboratory animals. Clinical trials have revealed severe psychiatric complications following the administration of interferon that closely resemble those of AIDS related dementia. These symptoms include depression, paranoia as well as suicidal potential which usually resolve once therapy is stopped. An acid labile form of interferon has also been found at high levels in AIDS patients, many of whom are found amongst the drug abuse population. Using animal models, it has been found that alpha interferon is able to attenuate the behavioral manifestations of naloxone induced withdrawal from morphine. The proposed studies have been designed to further characterize and to extend the various reports that interferon has central nervous system effects, some of which can modulate the intensity of naloxone-induced withdrawal in morphine-dependent rats. The withdrawal model will be used in order to identify brain sites where interferon is active as well as to identify specific neurotransmitters that may be altered by interferon. In addition, behaviors that comprise the withdrawal response will be thoroughly evaluated. These studies have wide-ranging implications in both the basic science and clinical settings. A number of immune system products are now known to be active at the level of the brain and/or pituitary gland and so these studies will further our understanding of bidirectional pathways that link the brain with the immune system. They may also reveal that measures of immunologic status may have predictive value in determining the severity of withdrawal symptoms. A multidisciplinary approach to studying this question is proposed and includes individuals highly experienced in working with all of the varied aspects of this study.

干扰素 - 巨噬细胞和 B 淋巴细胞的产物 - 已被发现 在人类中枢神经系统水平上发挥作用 在实验动物中。 临床试验显示其患有严重的精神疾病 干扰素给药后出现的并发症 类似于艾滋病相关的痴呆症。 这些症状包括 抑郁、偏执以及自杀倾向通常会得到解决 一旦治疗停止。 干扰素的酸不稳定形式也已被 艾滋病患者体内的含量很高，其中许多人是艾滋病患者中的一员。 吸毒人群。 使用动物模型发现，α 干扰素能够减弱纳洛酮的行为表现 诱导吗啡戒断。 拟议的研究旨在进一步表征和 延伸干扰素对中枢神经系统有影响的各种报道 效应，其中一些可以调节纳洛酮诱导的强度 吗啡依赖大鼠的戒断反应。 将采用提现模式 为了识别干扰素活跃的大脑部位以及 识别可能被干扰素改变的特定神经递质。 此外，构成戒断反应的行为将是 彻底评估。 这些研究在基础科学领域都具有广泛的影响 和临床环境。 目前已知许多免疫系统产品 在大脑和/或垂体水平上活跃，等等 这些研究将进一步加深我们对双向途径的理解 将大脑与免疫系统联系起来。 他们还可能透露 免疫状态的测量可能具有预测价值 戒断症状的严重程度。 多学科方法 提出研究这个问题并包括个人高度 在本研究的各个方面都有丰富的工作经验。