METHAMPHETAMINE AND AIDS: TOXIC INTERACTIONS IN ANIMALS

我们建议的研究计划项目(PPG)：斯克里普斯研究甲基苯丙胺-神经艾滋病研究计划(TSRI-MANARP)寻求在选定的动物模型中确定甲基苯丙胺(METH)神经药理学的神经毒性感染。使用临床前模型(小鼠、猫和猕猴)，我们将确定我们假设的常见病理过程的位置、生物学过程和功能后果，这些过程会导致更猛烈的病毒注射和治疗动物的功能下降。我们相信，只有采用拟议的实验计划中提供的受控实验环境，才能识别精确的生物相互作用和病理学的风险因素。利用三种公认的神经艾滋病动物模型，我们建议研究几种甲基苯丙胺的神经药理学和神经艾滋病相关的神经毒性。每一种动物模型都会导致这些有毒表型的趋同。修订后的申请中包括的初步数据为甲基苯丙胺神经药理学和艾滋病毒-1发病机制的协同作用提供了新的证据；这一证据得到了以下主题的支持：1.甲基苯丙胺对疾病进展和功能病理学的作用，在我们记录的与甲基苯丙胺滥用相关的艾滋病毒-1暴露的高危行为中；2.皮质下和皮质下与这两种药物独立相关的病理证据；3.苯丙胺对免疫状态直接作用的证据，以及4.这一领域的细胞、行为和病理生理学研究的悲观表现。

Our proposed Research Program Project (PPG): The SCRIPPS Research in-MethAmphetamine-NeuroAIDS Research Program (TSRI-MANARP) seeks to determine in select animal models, the neurotoxic infection with methamphetamine (METH) neuropharmacology. Using pre-clinical models (mice, felines and macaques), we will determine the location, biological course, and functional consequence of what we hypothesize to be common pathological processes leading to a more fulminant viral injection and functional decline in treated animals. We believe that only by employing the controlled experimental settings provided in the proposed experimental plan will the precise biological interactions and risk factors for pathology be discerned. Employing three well established animal models of neuro-AIDS we propose to investigate several methamphetamine neuropharmacology and NeuroAIDS-related neurotoxicity. Each animal model brings to convergence of these toxic phenotypes. Preliminary data included with the revised application provides new evidence for synergy in METH neuropharmacology and HIV-1 pathogenesis; evidence that is bolstered by theme to investigate the role of methamphetamine on disease progression and functional pathology in our documented high risk behaviors for HIV-1 exposure associated with methamphetamine abuse; 2. The converging evidence of both sub-cortical and cortical pathologies independently associated with both agents; 3. The evidence of direct actions of amphetamines on immune status, and 4. The woeful under representation of cellular, behavioral, and pathophysiological studies in this area.