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首页> 外文会议>Recent advances in clinical medicine >Prenatal stress perturbs nucleus accumbens glutamate signaling: Relation to heightened addiction vulnerability?
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Prenatal stress perturbs nucleus accumbens glutamate signaling: Relation to heightened addiction vulnerability?

机译：产前应激扰动伏隔核谷氨酸信号：与成瘾易感性增加有关？

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摘要

Growing attention has focused on individual differences in vulnerability to substance abuse disorders with both clinical and preclinical data indicating that life stress history and gender differences contribute to both the patterns of drug taking and in the propensity to relapse. Preclinical data indicates that female rats exhibit higher motivation to self-administer cocaine or alcohol and higher non-reinforced cocaine- or alcohol-seeking behavior under a variety of conditions (time-out responding, extinction, and reinstatement) compared to their male counterparts. Conversely, prenatal stress in males alters brain reward circuits to enhance self-administration of cocaine and alcohol, as well as, exhibit higher cocaine-seeking behavior under extinction and reinstatement conditions. However, the molecular substrates mediating enhanced cocaine- and alcohol-seeking due to stress histories and sex differences are unknown. The focus of our work is to determine the impact of sex and prenatal stress on glutamate neurotransmission within the nucleus accumbens—a neural substrate that is necessary and sufficient for cocaine-seeking behavior under a variety of conditions—and the relation of these alterations to drug-seeking behavior. To date, our findings suggest that (1) heightened drug-seeking in females may be related to elevated NMDA receptor levels, (2) heightened drug-seeking in prenatal stressed males may be related to elevated mGluR levels, (3) and the lack of effect of prenatal stress in females may be mediated by a compensatory reduction in Homerlb/c levels. These findings suggest molecular bases underlying individual differences in addiction vulnerability and provide molecular targets to modulate addiction vulnerability.
机译：越来越多的注意力集中在针对药物滥用疾病的易感性方面的个体差异，其临床和临床前数据均表明，生活压力史和性别差异有助于吸毒方式和复发倾向。临床前数据表明，与雄性大鼠相比，雌性大鼠在各种条件下（超时反应，消光和恢复）在自我管理可卡因或酒精方面表现出更高的动机，并且在非强化状态下对可卡因或酒精的寻求行为更高。相反，男性的产前压力改变了大脑的奖励回路，以增强可卡因和酒精的自我管理，并且在灭绝和恢复环境下表现出更高的可卡因寻觅行为。但是，由于应激史和性别差异而介导的可卡因和酒精吸收增强的分子底物是未知的。我们的工作重点是确定性别和产前压力对伏隔核内谷氨酸神经传递的影响，伏特核是多种条件下寻求可卡因行为的必要和充分的神经底物，以及这些改变与药物的关系寻求行为。迄今为止，我们的发现表明：（1）女性寻求药物的增加可能与NMDA受体水平升高有关；（2）产前紧张男性的寻求药物的增加可能与mGluR水平升高有关；（3）和缺乏女性代孕压力的影响可能是由Homerlb / c水平的代偿性降低所介导的。这些发现提示成瘾易感性个体差异的潜在分子基础，并提供了调节成瘾易感性的分子靶标。

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  • 来源
    《Recent advances in clinical medicine》|2010年|p.299-303|共5页
  • 会议地点 Cambridge(GB);Cambridge(GB);Cambridge(GB);Cambridge(GB);Cambridge(GB);Cambridge(GB);Cambridge(GB);Cambridge(GB)
  • 作者

    TOD E. KIPPIN; BASTIAN SPURTH; JOANNALEE C. CAMPBELL;

  • 作者单位

    Department of Psychology and the Neuroscience Research InstituternUniversity of California at Santa BarbararnPsychology Building, UCen Road, Santa Barbara, CaliforniarnUnited States of America;

    Department of Psychology and the Neuroscience Research InstituternUniversity of California at Santa BarbararnPsychology Building, UCen Road, Santa Barbara, CaliforniarnUnited States of America;

    Department of Psychology and the Neuroscience Research InstituternUniversity of California at Santa BarbararnPsychology Building, UCen Road, Santa Barbara, CaliforniarnUnited States of America;

  • 会议组织
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 临床医学;
  • 关键词

    prenatal stress; drug-seeking; cocaine; alcohol; nucleus accumbens; glutamate;

    机译：产前压力寻求毒品可卡因;醇;伏隔核谷氨酸;

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