RETROVIRAL EFFECT ON BEHAVIORAL RESPONSE TO ABUSED DRUGS

描述：（申请人摘要） 药物滥用和HIV-1感染的可能性密切相关。许多 滥用药物损害免疫功能，增加感染风险 暴露以及加速逆转录病毒的增殖。小 关于逆转录病毒感染对受试者的影响， 对给药的反应。目前尚不清楚HIV-1感染是否 增大降低或不影响使用者对药物效力的感知 和功效。该实验室已广泛使用LP-BM 5逆转录病毒 艾滋病的模拟小鼠研究认知和行为的影响， 逆转录病毒感染LP-BM_5感染诱导的小鼠艾滋病（MAIDS） 产生快速和离散的学习和记忆障碍，以及 CNS功能的改变。这种损害是在 MAIDS诱导的神经功能缺损的出现表明， 由获得或提取的损伤而不是运动损伤引起 性能我们最近已经证明，这些老鼠可以被训练成 在鼻戳中区分苯环利定和盐水。水奖励制度 灵敏（Eve = 3 mg/kg）、稳健（> 80%正确响应）和特异性 方式经LP-BM_5逆转录病毒感染后， 苯环利定增加10倍而对功效或特异性没有影响。我们 建议确定用LP-BM 5感染C57 BI/6 b小鼠是否 逆转录病毒改变了内感受性受体的效力、功效或特异性。 与药物滥用相关的药理学线索的辨别。因此我们 将研究逆转录病毒感染对小鼠能力的影响， 检测和应对常见的药物滥用，如苯环己哌啶，乙醇， 鸦片和可卡因此外，我们将研究LP-BM 5的作用， 感染对苯二氮卓类等其他药物滥用的反应， 巴比妥类药物。每月采集一次血液样本进行RT-PCR LP-BM 5滴度分析。重复测量ANOVA将用于统计 感染前后药物敏感性分析。此外，回归 作为RT-PCR衍生的病毒的函数的药物行为效应的分析 滴度将决定病毒载量和药物敏感性之间的关系。 这些研究将：l）提供关于逆转录病毒影响的基本信息 感染，如LP-BM 5或HIV-1对生物体的敏感性 滥用药物的主观影响; 2）使我们能够缩小 逆转录病毒感染的神经生物学效应的未来研究 这是行为相关的，并：3）提供一个具体的重点，为未来 HIV-1感染对受试者的影响 对人类滥用药物的反应。

DESCRIPTION: (Applicant's Abstract) Substance abuse and liability for HIV-1 infection are closely related. Many abused drugs impair immune function increasing the risk of infection per exposure as well as accelerating the proliferation of the retrovirus. Little is known regarding the effects of retroviral infection on the subjective response to drug administration. It is not clear whether HIV-1 infection increases. decreases or does not affect the user's perception of drug potency and efficacy. This laboratory has made extensive use of the LP-BM5 retroviral analog of AIDS in mice to study the cognitive and behavioral effects of retroviral infection. The murine AIDS (MAIDS) induced by LP-BM5 infection produces rapid and discrete impairment of learning and memory as well as alterations in CNS function. This impairment is produced well before the appearance of MAIDS-induced neurological deficits indicating that deficits result from impairment of acquisition or retrieval rather than motor performance. We have recently demonstrated that these mice can be trained to discriminate phencyclidine from saline in a nose poke. water reward system in a sensitive (Eve = 3mg/kg), robust (> 80% correct response) and specific manner. After in~ction with the LP-BM5 retrovirus, the potency of phencyclidine increases 10-fold with no effect on efficacy or specificity. We propose to determine whether infection of C57BI/6b mice with the LP-BM5 retrovirus alters the potency, efficacy, or specificity of interoceptive discrimination of pharmacological cues relevant to substance abuse. Thus, we will examine the effects of retroviral infection on the ability of mice to detect and respond to common drugs of abuse such as phencyclidines, ethanol, opioids and cocaine. In addition, we will examine the effects of LP-BM5 infection on the response to other drugs of abuse such as benzodiazepines and barbiturates. At monthly intervals, blood samples will be drawn for RT-PCR analysis of LP-BM5 titer. Repeated-measures ANOVA will be used for statistical analysis of pre-and post-infection drug sensitivity. In addition, regression analysis of drug behavioral effects as a function of RT-PCR-derived viral titer will determine the relationship between viral load and drug sensitivity. These studies will: l) provide basic information of the effects of retroviral infections such as LP-BM5 or HIV-l on the sensitivity of organisms to the subjective effects of drugs of abuse; 2) permit us to narrow the focus of future studies of the neurobiological effects of retroviral infection to sites which are behaviorally relevant and: 3) provide a specific focus for future collaborative studies of the effects of HIV- l infection on the subjective response to drugs of abuse in humans.