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奖励与成瘾的遗传学和基因组学研究方法。

Genetic and genomic approaches to reward and addiction.

作者信息

Mohn Amy R, Yao Wei-Dong, Caron Marc G

机构信息

Department of Cell Biology, HHMI Laboratories, Duke University Medical Centre, Box 3287, CARL Building, Durham, NC 27710, USA.

出版信息

Neuropharmacology. 2004;47 Suppl 1:101-10. doi: 10.1016/j.neuropharm.2004.07.025.

DOI:10.1016/j.neuropharm.2004.07.025
PMID:15464129
Abstract

Drug addiction is recognized as a mental disease affecting the brain's natural reward system. Drugs of abuse strongly activate reward structures in the brain and induce lasting changes in behavior that reflect changes in neuron physiology and biochemistry. With the ultimate goal of developing therapeutic interventions, it is of interest to determine the molecular and cellular components of motivation and reward, and identify those gene products that contribute to the process of drug addiction. Our laboratory has chosen three general genetic approaches to examine reward and addiction: reverse genetics to assess the role of candidate genes in drug responsiveness, forward genetics to discover novel regulators of dopamine transmission, and gene expression profiling to define gene sets in different brain structures that contribute to the molecular and neurobiological basis of reward.

摘要

药物成瘾被认为是一种影响大脑自然奖赏系统的精神疾病。滥用药物会强烈激活大脑中的奖赏结构,并诱发行为上的持久变化,这些变化反映了神经元生理和生物化学的改变。为了开发治疗干预措施这一最终目标,确定动机和奖赏的分子和细胞成分,并识别那些促成药物成瘾过程的基因产物是很有意义的。我们实验室选择了三种一般的遗传学方法来研究奖赏和成瘾:反向遗传学来评估候选基因在药物反应性中的作用,正向遗传学来发现多巴胺传递的新调节因子,以及基因表达谱分析来定义不同脑结构中有助于奖赏的分子和神经生物学基础的基因集。

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1
Genetic and genomic approaches to reward and addiction.奖励与成瘾的遗传学和基因组学研究方法。
Neuropharmacology. 2004;47 Suppl 1:101-10. doi: 10.1016/j.neuropharm.2004.07.025.
2
Drug addiction. Part II. Neurobiology of addiction.药物成瘾。第二部分。成瘾的神经生物学
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3
Sex differences in the neurobiology of drug addiction.药物成瘾神经生物学中的性别差异。
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The Brain on Drugs: From Reward to Addiction.《毒品与大脑:从奖赏到成瘾》
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Addiction and the brain: the neurobiology of compulsion and its persistence.成瘾与大脑:强迫行为及其持续性的神经生物学
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Dopamine and drug addiction: the nucleus accumbens shell connection.多巴胺与药物成瘾:伏隔核壳部的联系
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Molecular genetic probing of dopamine receptors in drug addiction.药物成瘾中多巴胺受体的分子遗传学探究
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Neuro-chemical activation of brain reward meso-limbic circuitry is associated with relapse prevention and drug hunger: a hypothesis.大脑奖励中边缘回路的神经化学激活与预防复发和药物渴求有关:一种假说。
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Effects of dopamine and glutamate on synaptic plasticity: a computational modeling approach for drug abuse as comorbidity in mood disorders.多巴胺和谷氨酸对突触可塑性的影响:一种用于情绪障碍共病药物滥用的计算建模方法。
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Addiction and its brain science.成瘾及其脑科学。
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Attenuation of cocaine-induced conditioned locomotion is associated with altered expression of hippocampal glutamate receptors in mice lacking LPA1 receptors.缺乏 LPA1 受体的小鼠中海马谷氨酸受体表达改变与可卡因诱导的条件性运动减弱有关。
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Cocaine modulates both glutaminase gene expression and glutaminase activity in the brain of cocaine-sensitized mice.可卡因可调节可卡因敏化小鼠大脑中的谷氨酰胺酶基因表达和活性。
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Gene expression changes following extinction testing in a heroin behavioral incubation model.海洛因行为性潜伏模型中消退测试后的基因表达变化
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Reduced D2-mediated signaling activity and trans-synaptic upregulation of D1 and D2 dopamine receptors in mice overexpressing the dopamine transporter.多巴胺转运体过表达小鼠中D2介导的信号传导活性降低以及D1和D2多巴胺受体的跨突触上调。
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Enhanced cocaine responsiveness and impaired motor coordination in metabotropic glutamate receptor subtype 2 knockout mice.代谢型谷氨酸受体2基因敲除小鼠对可卡因反应增强及运动协调性受损
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