BEHAVIORAL DETERMINANTS OF OPIOID/IMMUNE INTERACTIONS

尽管大量证据表明阿片类药物 和免疫系统，很少有研究调查的作用 行为和环境变量在这种相互作用。 一个变量 对了解长期类阿片使用和复吸特别重要 与阿片类药物给药的许多作用 而戒断反应可以受到环境刺激的影响。 因此，很可能是免疫功能的改变， 由于急性和长期阿片类药物给药而发生 也可能成为条件性的，因此有可能持续下去， 在阿片类药物使用停止后很久。 因此，我们的目标是 检查阿片类药物诱导的免疫功能改变，重点是 行为，环境和药理学变量在这些中的作用 交互. 我们的第一个具体目标提供了背景信息， 这些研究通过探索急性和 慢性阿片类药物给药。 这些调查包括一系列 阿片类激动剂吗啡剂量，急性给药（每日一次） 或慢性（每日一剂，持续1、3、5或更多天）。 免疫功能 将通过几种不同的啮齿动物体外试验进行评估，包括 脾、淋巴结和全血淋巴细胞的有丝分裂原刺激， 自然杀伤细胞测定，白细胞介素-1、白细胞介素-2和 干扰素产生和流式细胞术分析，以评估 白细胞亚群 抗体的其他体内测量 生产也将被使用。 我们的第二个具体目标是审查 条件反射在阿片诱导的免疫功能改变中的作用。 鉴于之前的证据表明，刺激与阿片类药物配对 给药可引起阿片样物质的许多体征和症状， 以及调节对阿片类药物耐受性的发展 影响，我们将确定是否刺激与吗啡将 诱导免疫功能的吗啡样改变（在缺乏 吗啡）以及与吗啡给药相关的刺激是否 会调节吗啡对免疫功能的影响 保留 免疫功能中这些条件性改变的消失将 也要检查。 我们的第三个具体目标是研究 吗啡诱导的免疫改变之间的相互作用 功能和行为/环境事件。 这些研究将采用 选择性拮抗剂，以检查阿片样物质和儿茶酚胺能 阿片类药物诱导的免疫功能改变的系统。 在所有研究中， 药理学变量，如吗啡的剂量和持续时间， 将评估吗啡给药以及 行为/环境变量，如条件反射的性质 环境，条件试验的次数和预暴露于 条件刺激

Although a wealth of evidence suggests an interaction between the opioid and immune systems, very few studies have investigated the role of behavioral and environmental variables in this interaction. One variable of particular importance in understanding long-term opioid use and relapse relates to the ease with which many of the effects of opioid administration and withdrawal can be conditioned to stimuli in the environment. Accordingly, it is likely that the alterations in immune function which occur as the result of acute as well as long-term opioid administration might also become conditioned and therefore have the potential to persist long after opioid use has been terminated. Thus, it is our objective to examine opioid-induced alterations in immune function with emphasis on the role of behavioral, environmental, and pharmacological variables in these interactions. Our first specific aim provides background information for these investigations by exploring the unconditioned effects of acute and chronic opioid administration. These investigations include a range of doses of the opioid agonist morphine, given either acutely (one daily dose) or chronically (one daily dose for 1,3,5 or more days). Immune function will be assessed with several different rodent in vitro assays, including mitogen-stimulation of splenic, lymph node and whole-blood lymphocytes, a natural-killer cell assay, assessment of interleukin-1, interleukin-2 and interferon production and flow cytometry analysis to assess alterations in leukocyte subpopulations. Additional in vivo measures of antibody production will also be employed. Our second specific aim examines the role of conditioning in opioid-induced alterations in immune function. Given previous demonstrations that stimuli paired with opioid administration can elicit many of the signs and symptoms of opioid administration as well as modulate the development of tolerance to opioid effects, we will determine whether stimuli associated with morphine will induce morphine-like alterations in immune function (in the absence of morphine) and also whether stimuli associated with morphine administration will modulate the effects morphine has on immune function. The retention and extinction of these conditioned alterations in immune function will also be examined. Our third specific aim investigates the mechanisms which underlie interactions between morphine-induced alterations in immune function and behavioral/environmental events. These studies will employ selective antagonists to examine the role of opioid and catecholaminergic systems in opioid-induced alterations in immune function. In all studies, pharmacological variables such as dose of morphine, and duration of morphine administration will be assessed as well as behavioral/environmental variables such as the nature of the conditioning environment, the number of conditioning trials and preexposure to the conditioning stimuli.