BEHAVIORAL DETERMINANTS OF OPIOID/IMMUNE INTERACTIONS

尽管大量证据表明阿片类药物之间的相互作用 和免疫系统，很少有研究调查它的作用 这种相互作用中的行为和环境变量。一个变量 在了解长期使用阿片类药物和复发方面特别重要 与阿片类药物给药的许多效果 而戒断可以根据环境中的刺激来调节。 因此，免疫功能的改变很可能是 由于急性和长期服用阿片类药物而发生 也可能成为条件性的，因此有可能持续下去 在阿片类药物停止使用很久之后。因此，我们的目标是 检查阿片类药物诱导的免疫功能变化，重点是 行为、环境和药理学变量在这些变化中的作用 互动。我们的第一个具体目标是提供背景信息 这些研究通过探索急性和非传染性疾病的无条件影响 长期服用阿片类药物。这些调查包括一系列 阿片激动剂吗啡的剂量，急性给药(每天一次) 或慢性给药(每日一剂，连服1、3、5天或更多)。免疫功能 将用几种不同的啮齿动物体外试验进行评估，包括 有丝分裂原对脾、淋巴结和全血淋巴细胞的刺激作用 自然杀伤细胞试验、白介素1、白介素2和 干扰素产生和流式细胞术分析以评估细胞的变化 白细胞亚群。体内抗体的额外测量 还将雇用生产人员。我们的第二个具体目标是检查 条件反射在阿片类药物诱导的免疫功能改变中的作用。 鉴于之前的演示，刺激物与阿片类药物配对 服药可引起阿片类药物的许多体征和症状 给药以及调节对阿片类药物耐受性的发展 影响，我们将确定与吗啡相关的刺激是否会 诱导免疫功能出现类吗啡改变(在缺乏 吗啡)，以及与吗啡给药有关的刺激 会调节吗啡对免疫功能的影响。留存 而这些免疫功能的条件性变化的消失将 也要接受检查。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。这些研究将使用 选择性拮抗剂研究阿片和儿茶酚胺能的作用 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 将评估吗啡的使用情况以及 行为/环境变量，如条件反射的性质 环境、条件化试验的次数和预先暴露于 条件性刺激。

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.