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首页> 外文期刊>Brain research >Increases in compulsivity, inflammation, and neural injury in HIV transgenic rats with escalated methamphetamine self-administration under extended-access conditions
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Increases in compulsivity, inflammation, and neural injury in HIV transgenic rats with escalated methamphetamine self-administration under extended-access conditions

机译:在延长接入条件下,HIV转基因大鼠的强制性,炎症和神经损伤的增加

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摘要

The abuse of stimulants, such as methamphetamine (METH), is associated with treatment non-compliance, a greater risk of viral transmission, and the more rapid clinical progression of immunological and central nervous system human immunodeficiency virus (HIV) disease. The behavioral effects of METH in the setting of HIV remain largely uncharacterized. We used a state-of-the-art paradigm of the escalation of voluntary intravenous drug self-administration in HIV transgenic (Tg) and wildtype rats. The rats were first allowed to self-administer METH under short-access (ShA) conditions, which is characterized by a nondependent and more "recreational" pattern of METH use, and then allowed to self-administer METH under long-access (LgA) conditions, which leads to compulsive (dependent) METH intake. HIV Tg and wildtype rats self-administered equal amounts of METH under ShA conditions. HIV Tg rats self-administered METH under LgA conditions following a 4-week enforced abstinence period to model the intermittent pattern of stimulant abuse in humans. These HIV Tg rats developed greater motivation to self-administer METH and self-administered larger amounts of METH. Impairments in function of the medial prefrontal cortex (mPFC) contribute to compulsive drug and alcohol intake. Gene expression profiling of the mPFC in HIV Tg rats with a history of escalated METH self-administration under LgA conditions showed transcriptional evidence of increased inflammation, greater neural injury, and impaired aerobic glucose metabolism than wildtype rats that self-administered METH under LgA conditions. The detrimental effects of the interaction between neuroHlV and escalated METH intake on the mPFC are likely key factors in the greater vulnerability to excessive drug intake in the setting of HIV.
机译:滥用兴奋剂(例如甲基苯丙胺(甲基))与治疗不合规有关,病毒传播风险更大,以及免疫和中枢神经系统人类免疫缺陷病毒(HIV)疾病的更快临床进展。艾滋病病毒含量的行为效应在很大程度上仍然很大。我们在HIV转基因(TG)和Wildtype大鼠中,使用了术语自愿静脉内药物自我施用的最新范式。首先使大鼠在短期访问(SHA)条件下自我施用,其特征在于,其特征在于偏离和更多的“娱乐”模式,然后允许在长途接入(LGA)下自我施用甲基条件,导致强迫(依赖)的甲基摄入量。 HIV TG和Wildtype大鼠在SHA条件下自我管理等量的甲基。艾滋病毒TG大鼠在LGA条件下自我施用,在4周的强制禁止期后,以模拟人类兴奋剂滥用的间歇模式。这些HIV TG大鼠对自我施用的甲基和自我施用的较大量的甲基溶液产生了更大的动力。内侧前额叶皮质(MPFC)的功能损伤有助于强迫药物和酒精摄入量。在LGA条件下,HIV TG大鼠MPFC的基因表达分析在LGA条件下升级的升级性血液施用历史,显示出增加炎症,更高的神经损伤和有氧葡萄糖代谢的有氧葡萄糖代谢的转录证据比在LGA条件下自我施用的氨基甲醇。在MPFC上对MPFC的逐渐升高的甲基摄入之间的相互作用的不利影响可能是艾滋病毒环境中过度药物摄入量大的脆弱性的关键因素。

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  • 来源
    《Brain research》 |2020年第2020期|共11页
  • 作者单位

    Scripps Res Inst Dept Neurosci La Jolla CA 92037 USA;

    Scripps Res Inst Dept Immunol &

    Microbiol La Jolla CA 92037 USA;

    Scripps Res Inst Dept Immunol &

    Microbiol La Jolla CA 92037 USA;

    Scripps Res Inst Dept Immunol &

    Microbiol La Jolla CA 92037 USA;

    Scripps Res Inst Dept Immunol &

    Microbiol La Jolla CA 92037 USA;

    Scripps Res Inst Dept Immunol &

    Microbiol La Jolla CA 92037 USA;

    Scripps Res Inst Dept Immunol &

    Microbiol La Jolla CA 92037 USA;

    Baylor Coll Med Dept Pediat Dan L Duncan Canc Ctr Houston TX 77030 USA;

    Univ Maryland Baltimore MD 21201 USA;

    Scripps Res Inst Dept Neurosci La Jolla CA 92037 USA;

    Baylor Coll Med Dept Pediat Dan L Duncan Canc Ctr Houston TX 77030 USA;

    Scripps Res Inst Dept Immunol &

    Microbiol La Jolla CA 92037 USA;

    Scripps Res Inst Dept Immunol &

    Microbiol La Jolla CA 92037 USA;

    Scripps Res Inst Dept Immunol &

    Microbiol La Jolla CA 92037 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 神经病学;
  • 关键词

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