OPIOID PROPERTIES OF INTERFERON

干扰素的阿片类药物特性

• 批准号: 3069551
• 负责人: NICHOLAS R HALL
• 金额: $ 6.45万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-06-01 至 1996-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3069551
• 关键词: Newcastle disease virus; analgesia; biological models; body temperature regulation; brain mapping; catecholamines; chemical stimulation; dosage; drug tolerance; drug withdrawal; histology; interferon alpha; interferon inducers; interleukin 1; laboratory rat; morphine; naloxone; narcotics; neuroimmunomodulation; neuropeptides; neuropharmacology; neurotransmitters; operant conditionings; psychological reinforcement; psychoneuroimmunology; statistics /biometry; thymosin

This is a request for a continuation of RSDA Level 11 support which was originally provided to evaluate the effects of thymic peptides on central nervous system (CNS) function. The original study has now evolved to include assessment of the CNS effects of interferon alpha which appears to have opioid-like properties. Although all aspects of interferon's effects are of interest, we are focusing upon its ability to attenuate naloxone precipitated withdrawal symptoms in morphine-dependent rats. This model is being used to identify specific brain sites where interferon is active as well as neurotransmitter systems that may be involved. In addition, the component behaviors of withdrawal will be carefully evaluated in order to gain insights as to where and how the CNS effects of this cytokine are mediated. RSDA support is being sought in order to make available the time and resources to become more proficient in the area of neuropharmacology. This will be done by spending time in the laboratory of Dr. Martin Adler who is a consultant to the currently funded R01 grant. I also wish to begin evaluating changes in neurotransmitters and neuropeptides using in vitro perifusion and the push-pull cannula technique which I will need to learn. This will be accomplished through collaborations with Dr. Chris Phelps with whom I am already collaborating. The net result will be a more sensitive assessment of the neurochemical effects of interferon alpha as well as more versatility in expanding upon the future directions that this project will take. These studies have wide ranging implications in the areas of AIDS and drug abuse. Clinical trials have revealed severe psychiatric complications following the administration of interferon which have some similarities to the symptoms of AIDS related dementia. These include depression, paranoia as well as suicidal potential which usually resolve once the therapy is stopped. An acid labile form of interferon has been found at high levels in AIDS patients and may well be contributing to some of the CNS symptoms. In the context of drug abuse, it is possible that measures of immunologic status may have predictive value in determining the severity of withdrawal symptoms in addition to furthering our understanding of the bidirectional links between the CNS and the immune system.

这是请求继续提供 RSDA 11 级支持， 最初是为了评估胸腺肽对 中枢神经系统（CNS）功能。 最初的研究现在已经发展了 包括对干扰素α的中枢神经系统影响的评估，该影响似乎 具有类似阿片类药物的特性。 虽然干扰素的各个方面 影响很有趣，我们关注的是它减弱的能力 纳洛酮会导致吗啡依赖大鼠出现戒断症状。 这 模型被用来识别干扰素所在的特定大脑部位 可能涉及的活性系统和神经递质系统。 在 此外，将仔细评估退出行为的组成部分 为了深入了解中枢神经系统在何处以及如何影响这一点 细胞因子介导。 正在寻求 RSDA 支持，以便提供时间和 资源变得更加精通神经药理学领域。 这 将通过花时间在马丁阿德勒博士的实验室来完成，他是 目前资助的 R01 赠款的顾问。 我也想开始 使用体外评估神经递质和神经肽的变化 我需要学习灌注和推拉插管技术。 这将通过与 Chris Phelps 博士的合作来完成 我已经在和谁合作了。 最终结果将更加敏感 评估干扰素α等的神经化学作用 扩展该项目未来方向的多功能性 拿。 这些研究在艾滋病和艾滋病领域具有广泛的影响 药物滥用。 临床试验显示严重的精神并发症 与干扰素有一些相似之处的给药后 艾滋病相关痴呆症的症状。 这些包括抑郁症、偏执狂 以及自杀倾向，一旦治疗完成，通常就会消失 停了下来。 已发现高浓度的酸不稳定形式的干扰素 在艾滋病患者中，很可能会导致一些中枢神经系统症状。 在药物滥用的情况下，免疫学措施有可能 状态可能对确定戒断严重程度具有预测价值 症状除了进一步加深我们对双向的理解 中枢神经系统和免疫系统之间的联系。