AIDS & OPIATES MONKEY MODEL

由于已知外源性和内源性阿片类药物可以调节 免疫功能，阿片类药物滥用是导致 人类艾滋病，有理由怀疑鸦片类药物本身会影响 艾滋病的进展。因为这个问题不能得到充分解决 在人类或小动物模型中，我们建议通过一种 猴子模型是艾滋病最合适的动物模型 学习，也是一个强大的成瘾模型。我们的初步数据 来自其他实验室的数据表明，鸦片类药物的影响 艾滋病的进展是有条件的，具有不同的保护性和 恶化效应取决于体内平衡的稳定性 阿片类药物依赖和感染的毒性 免疫缺陷病毒(SIV)。因此，建议进行的研究如下 意在以一种有统计学意义的方式测试保护性 我们之前在一项初步研究中观察到的影响是真实的。这些 数据将补充正在进行的研究S在她的实验室寻找 在一些不同的模型中发现潜在的加重效应 比我们使用的毒力更强的病毒株(SIVmac239与我们的SIVsmm9)， 在一个不太稳定的阿片类药物依赖环境中。 计划中的研究还将检查一些免疫神经内分泌。 对鸦片类药物暴露和轻微压力的反应发生的变化，在 一种动态的时尚，这样这些变化就可以与 预计会影响阿片剂保护环境的情况 依赖的猴子对抗SIV。最特别的是，我们将测试我们的 保护效果受能力影响的假说 阿片类药物以某种方式调节T细胞和其他白细胞的运输 这在T细胞亚型之间建立了平衡，有利于 抵抗病毒感染的进展。这些研究， 因此，可能会对公共卫生和治疗产生重大影响 在处理艾滋病/药物滥用两难境地方面。为NIDA/NIH提供资金 $360,868 2/01/97-1/31/99出版物，R.M.和Vlahov，D. 阿片类药物在HIV-1感染进展中的潜在辅助因素 艾滋病。神经免疫杂志83：77-87,1998。P51RR00165-38 1/1/1998- 12/31/1998耶克斯地区灵长类研究中心

Since exogenous and endogenous opioids are known to modulate immune functions, and opiate abuse is a major etiologic factor in human AIDS, there is reason to suspect that opiates themselves affect progression of AIDS. Since this issue cannot be addressed adequately in human or small animal models, we are proposing to address it with a monkey model that is the most appropriate animal model for AIDS studies and is also a powerful addiction model. Our preliminary data and data from other laboratories suggest that the effects of opiates on progression of AIDS are conditional, having variably protective and exacerbatory effects depending on the homeostatic stability of the opiate dependency and also the virulence of the infecting immunodeficiency virus (SIV). Accordingly, the proposed studies are meant to test in a statistically meaningful way whether the protective effects we previously observed in a pilot study are genuine. These data will complement ongoing studie s in anot her laboratory looking at potential exacerbatory effects in a somewhat different model using a more virulent virus strain than we use (SIVmac239 vs our SIVsmm9), in a less homeostatically stabilizing opiate dependency environment. The planned studies will also examine a number of immunoneuroendocrine changes that occur in response to opiate exposure and mild stress, in a kinetic fashion, so that these changes can be related to circumstances projected to affect a protective environment for opiate dependent monkeys against SIV. Most particularly, we will test our hypothesis that the protective effects are influenced by the ability of opiates to modulate T-cell and other leukocyte trafficking in a way that establishes a balance between T-cell subtypes that favors resistance to progression of the viral infection. These studies, therefore, may have significant public health and therapeutic impact in dealing with the AIDS/drug-abuse dilemma. FUNDING NIDA / NIH $360,868 2/01/97 - 1/31/99 PUBLICATIONS Donahoe, R.M. and Vlahov, D. Opiates as potential cofactors in progression of HIV-1 infections to AIDS. J Neuroimmunol 83:77-87, 1998. P51RR00165-38 1/1/1998 - 12/31/1998 Yerkes Regional Primate Research Center