FIV--A LENTIVIRUS MODEL FOR OPIATE EFFECTS ON DISEASE

在这项提案中，我们计划应用和进一步开发FIV/CAT系统 成为研究药物滥用对慢病毒影响的模型 疾病的发展。我们将在体外检测吗啡对小鼠心脏功能的影响。 FIV复制率和转录率。我们亦建议研究 阿片类药物对FIV感染者神经系统形态的影响 猫。有人建议，阿片类药物被运送到 动物可能会影响研究的最终结果。因此，我们计划 考察三种吗啡排期方法：单次注射、多次注射 急性注射，以及不断升级的多次注射，导致慢性 吗啡依赖，然后是实验强制戒断。这个 这些药物方案中的每一个对FIV疾病进展的影响将是 由一组病毒学、免疫学和功能性中枢神经系统决定 化验。从这项研究中获得的信息将增强我们的 了解阿片类药物在慢病毒发病机制中的作用。至 真正了解疾病的发病机制及其影响因素，如 阿片类药物在这个过程中，最终必须进行研究 动物。我们已经将FIV/CAT系统开发为合法的模式 研究慢病毒对中枢神经系统的影响。因为静脉注射毒品 滥用已成为感染HIV-1最常见的方式， 更好地了解滥用药物可能对 慢病毒病的进展是迫切需要的。新技术的发展 FIV/CAT系统在药物滥用影响研究中的应用 慢病毒病的进展将提供一个有价值的工具来解决 这种潜在的重要相互作用。

In this proposal, we plan to apply and further develop the FIV/cat system into a model for the study of the effects of drug abuse on lentivirus disease progression. We will examine, in vitro, the effects of morphine on FIV replication and transcriptional rates. We also propose to examine the effects of opiates on the neurological form of the disease in FIV infected cats. It has been suggested that the manner that opiates are delivered to the animal may affect the ultimate outcome of the study. Thus, we plan to examine three morphine scheduling approaches: a single injection, multiple acute injections, and escalating multiple injections, leading to chronic morphine dependence, followed by experimentally enforced withdrawal. The effects of each of these drug schedules on FIV disease progression will be determined by a battery of virological, immunological and functional CNS assays. The information gained from this study will enhance our understanding of opiates as a co-factor in lentivirus pathogenesis. To truly understand disease pathogenesis and the effects co-factors like opiates have on the process, ultimately studies must be conducted in animals. We have developed the FIV/cat system into a legitimate model for studying the effects of lentiviruses on the CNS. Since intravenous drug abuse has become the most common mode of acquiring HIV-1 infections, a greater understanding of the potential effects that drug abuse may have on lentivirus disease progression is urgently needed. Development of the FIV/cat system into a model for the study of the effects of drug abuse on lentivirus disease progression will provide a valuable tool to address this potentially important interaction.