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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Increased vulnerability to cocaine in mice lacking dopamine D_3 receptors
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Increased vulnerability to cocaine in mice lacking dopamine D_3 receptors

机译：缺乏多巴胺D_3受体的小鼠对可卡因的脆弱性增加

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摘要

Neuroimaging studies using positron emission tomography suggest that reduced dopamine D-2 receptor availability in the neostriatum is associated with increased vulnerability to drug addiction in humans and experimental animals. The role of D_3 receptors (D_3Rs) in the neurobiology of addiction remains unclear, however. Here we report that D_3R KO (D_3~(-/-)) mice display enhanced cocaine self-administration and enhanced motivation for cocaine-taking and cocaine-seeking behavior. This increased vulnerability to cocaine is accompanied by decreased dopamine response to cocaine secondary to increased basal levels of extracellular dopamine in the nucleus accumbens, suggesting a compensatory response to decreased cocaine reward in D_3~(-/-) mice. In addition, D_3~(-/-) mice also display up-regulation of dopamine transporters in the striatum, suggesting a neuroadapta-tive attempt to normalize elevated basal extracellular dopamine. These findings suggest that D_3R deletion increases vulnerability to cocaine, and that reduced D_3R availability in the brain may constitute a risk factor for the development of cocaine addiction.
机译：使用正电子发射断层扫描的神经影像学研究表明，新纹状体中多巴胺D-2受体的可用性降低与人类和实验动物对药物成瘾的脆弱性增加有关。但是，D_3受体（D_3Rs）在成瘾的神经生物学中的作用仍不清楚。在这里，我们报告D_3R KO（D_3〜（-/-））小鼠显示出增强的可卡因自我管理和增强的可卡因服用和寻找可卡因行为的动机。对可卡因的这种增加的脆弱性伴随着伏伏核中细胞外多巴胺的基础水平增加而继发的对可卡因的多巴胺反应降低，这表明对D_3〜（-/-）小鼠可卡因奖励减少的补偿性反应。此外，D_3〜（-/-）小鼠在纹状体中也显示出多巴胺转运蛋白的上调，表明神经适应性尝试可以使升高的基础细胞外多巴胺正常化。这些发现表明，D_3R缺失增加了对可卡因的脆弱性，而大脑中D_3R可用性的降低可能构成可卡因成瘾发展的危险因素。

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  • 作者

    Rui Song; Hai-Ying Zhang; Xia Li; Guo-Hua Bi; Eliot L. Gardner; Zheng-Xiong Xi;

  • 作者单位

    Neuropsychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224,Neuropsychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224;

    Neuropsychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224;

    Neuropsychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224,Department of Psychiatry, School of Medicine, University of California at San Diego, La Jolla, CA 92093;

    Neuropsychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224;

    Neuropsychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224;

    Neuropsychopharmacology Section, Intramural Research Program, National Institute on Drug Abuse, Baltimore, MD 21224;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    etiology of addiction; susceptibility to cocaine; reinforcement; extinction; reinstatement;

    机译：成瘾的病因;对可卡因的敏感性;加强;灭绝复职;

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