METHAMPHETAMINE AND AIDS: TOXIC INTERACTIONS IN ANIMALS

我们提出的研究计划项目（PPG）：在MET-MANARP研究计划（TSRI-MANARP）的研究，旨在确定在选定的动物模型，与甲基苯丙胺（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为导致治疗动物中更暴发性病毒注射和功能下降的常见病理过程的位置、生物学过程和功能后果。我们认为，只有采用拟议实验计划中提供的受控实验设置，才能识别精确的生物相互作用和病理学风险因素。采用三种成熟的神经艾滋病动物模型，我们建议调查几个甲基苯丙胺的神经药理学和神经艾滋病相关的神经毒性。每种动物模型都使这些毒性表型趋于一致。修订后的申请中包含的初步数据为METH神经药理学和HIV-1发病机制的协同作用提供了新的证据;在我们记录的与甲基苯丙胺滥用相关的HIV-1暴露高危行为中，研究甲基苯丙胺对疾病进展和功能病理学的作用的主题支持了证据; 2.两种药物均独立相关的皮质下和皮质病理学的会聚证据; 3.安非他明对免疫状态的直接作用的证据，和4。这一领域的细胞、行为和病理生理学研究令人遗憾的不足。

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.