BEHAVIORAL FACTORS IN HEROIN'S EFFECT ON NITRIC OXIDE

中国的传染病发病率很高。 海洛因依赖者。尽管周围存在重大的健康问题 关于海洛因的使用，很少有研究研究海洛因对免疫状态的影响。一个 大量的最新数据表明，一氧化氮的诱导在 在对传染病的免疫反应中发挥关键作用。来自我们的新数据 实验室提供了第一个海洛因使用产生的证据 诱导型一氧化氮合酶(INOS)的变化 用于生产一氧化氮。我广泛地测试了特定的目标 海洛因引起体内表达广泛改变的假说 对NOS的支持。这一特定目的充分评估了海洛因对健康的影响 脂多糖诱导诱导型一氧化氮合酶表达。这些实验确立了 海洛因的量效关系及其拮抗作用 纳曲酮的疗效。为了测量活体内一氧化氮合酶的产生，我们使用了两种方法 RT-PCR和Western blotting检测iNOS mRNA表达和蛋白印迹的变化 脾、肺和肝组织中的蛋白质。我们还测量亚硝酸盐/硝酸盐 血浆。《特定目的II》验证了海洛因诱导的脑电活动改变的假设 一氧化氮合酶的产生受环境刺激和药物的影响 行政管理。证明免疫改变可以由 与海洛因使用有关的刺激很重要，因为它表明 吸食海洛因的有害健康后果是有条件的 环境刺激，而不仅仅是药物的药理特性。 拟议中的研究确定了海洛因对一氧化氮的影响 与海洛因配对的环境刺激可以引发生产 行政管理。控制程序被用来确保这些条件 改变是由条件过程本身造成的，而不是 条件反射过程中涉及的辅助因素。灭绝试验 而潜在的抑制效应将遵循以下原则 巴甫洛夫条件反射。特定的AimIII测试了药物 自我管理是控制海洛因使用的重要行为变量 对一氧化氮产生的影响。自我管理范式 为评估海洛因的临床相关性提供了一种方法学 对一氧化氮产生的影响。这项研究比较了海洛因的影响 自我给药转变为被动给药。调查 自服海洛因对一氧化氮产生的影响是由以下因素驱动的 有证据表明，对药品管理的控制大大影响了它的 生理效应。证明海洛因是不同的 在改变一氧化氮产生方面的有效性取决于药物是否 是自行给药还是被动输液对 海洛因使用的健康后果。总而言之，对 海洛因对诱导型一氧化氮合酶合成的调节作用 更好地了解阿片类药物如何影响免疫系统和 健康。

There is a high incidence of infectious disease in heroin-dependent individuals. In spite of the major health issues surrounding heroin use, few studies have examined the impact of heroin on immune status. A wealth of recent data has revealed that the induction of nitric oxide plays a critical role in the immune response to infectious diseases. New data from our laboratory has provided the first evidence that heroin administration produces alterations of inducible nitric oxide synthase (iNOS), the enzyme responsible for the production of nitric oxide. Specific Aim I extensively tests the hypothesis that heroin induces widespread alterations in the in vivo expression of NOS. This specific aim fully evaluates the effect of heroin on lipopolysaccaride (LPS)-induced iNOS expression. The experiments establish dose-effect relationships for heroin, as well as the antagonism of those effects with naltrexone. To measure NOS production in vivo, we employ both RT-PCR and western blotting to measure alterations of iNOS mRNA expression and protein in spleen, lung, and liver tissue. We also measure nitrite/nitrate in plasma. Specific Aim II tests the hypothesis that heroin-induced alteration of NOS production is conditioned to environmental stimuli paired with drug administration. The demonstration that immune alterations can be induced by the stimuli associated with heroin administration is important for it indicates that the detrimental health consequences of heroin use are conditioned to environmental stimuli and not solely the pharmacological property of the drug. The proposed studies determine whether heroin's effect on nitric oxide production can be elicited by environmental stimuli paired with heroin administration. Control procedures are used to assure that these conditioned alterations are due to conditioning processes per se, and not the result of ancillary factors involved in the conditioning procedure. Tests of extinction and latent inhibition will establish that the effects follow the principles of Pavlovian conditioning. Specific AimIII tests the hypothesis that drug self-administration is an important behavioral variable controlling heroin's effect on the production of nitric oxide. The self-administration paradigm provides a clinically relevant methodology for the assessment of heroin's effects on nitric oxide production. The study compares the effects of heroin self-administration to those of passive drug administration. Investigation of the effects of self-administered heroin on nitric oxide production is driven by evidence showing that control over drug administration greatly influence it's physiological effects. The demonstration that heroin is differentially efficacious in altering nitric oxide production depending upon whether the drug is self-administered or passively infused has important implications for the health consequences of heroin use. Collectively, the characterization of heroin-induced modulation of inducible nitric oxide synthase production provides a greater understanding of how opioids impact the immune system and health.