Behavioral effects of chronic methamphetamine treatment in HIV-1 gp120 transgenic mice.
Behavioral effects of chronic methamphetamine treatment in HIV-1 gp120 transgenic mice.
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DOI：
10.1016/j.bbr.2012.08.037
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发表时间：
2013-01-01
影响因子：
2.7
通讯作者：
Minassian, Arpi
中科院分区：
文献类型：
--
作者：
Henry, Brook L.;Geyer, Mark A.;Buell, Mahalah;Perry, William;Young, Jared W.;Minassian, Arpi
甲基苯丙胺（METH）依赖经常与艾滋病毒感染共病。这两种因素的独立特征是抑制缺陷，这可能表现为运动活动增加，不适当的持续行为，以及对新刺激的探索性反应升高，但METH暴露和HIV联合作用的影响尚不清楚。在这项研究中，我们给予慢性递增/狂欢方案的METH或车辆治疗野生型（WT）或转基因（tg）小鼠表达的HIV-1 gp 120包膜蛋白和量化的去抑制在7天内停药后。我们假设，与溶剂处理的WT或gp 120 tg动物相比，长期给予METH的gp 120 tg小鼠将表现出更明显的抑制缺陷。我们的研究结果表明，METH单独治疗增加了新的对象的相互作用，而女性METH治疗的gp 120 tg小鼠表现出最高水平的探索（holepoking）相比，其他雌性小鼠。转基因小鼠表现出更少的后腿相对于WT，略少的运动，也表现出更持久的运动模式的趋势。总之，METH治疗和gp 120表达都可能改变抑制，但这种作用是选择性的，并取决于年龄和性别的变化，可能会影响多巴胺和额纹状体功能。这些研究结果表明，需要提高我们对艾滋病毒和药物使用的综合影响的认识，并促进改善共病和药物依赖的治疗方法。
Methamphetamine (METH) dependence is frequently comorbid with HIV infection. Both factors are independently characterized by inhibitory deficits, which may manifest as increased motor activity, inappropriate perseverative behavior, and elevated exploratory responses to novel stimuli, but the effect of combined METH exposure and HIV is not well understood. In this study, we administered a chronic escalation/binge regimen of METH or vehicle treatment to wildtype (WT) or transgenic (tg) mice expressing the HIV-1 gp120 envelope protein and quantified disinhibition during the 7 days following drug withdrawal. We hypothesized that gp120tg mice administered chronic METH would exhibit more pronounced inhibitory deficits compared to vehicle-treated WT or gp120tg animals. Our results showed that METH treatment alone increased novel object interaction while female METH-treated gp120tg mice exhibited the highest level of exploration (holepoking) compared to other female mice. Transgenic mice exhibited fewer rears relative to WT, slightly less locomotion, and also demonstrated a trend towards more perseverative motor patterns. In summary, both METH treatment and gp120 expression may modify inhibition, but such effects are selective and dependent upon variations in age and sex that could impact dopamine and frontostriatal function. These findings illustrate the need to improve our knowledge about the combined effects of HIV and substance use and facilitate improved treatment methods for comorbid disease and drug dependence.
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