DOPAMINE TRANSPORTER-HUMAN & MOUSE GENES, DOPAMINERGIC DISORDERS & KNOCKOUT MICE

人类多巴胺转运蛋白

• 批准号: 6289590
• 负责人: George Richard Uhl
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6289590
• 关键词: animal genetic material tag; cocaine; dopamine; dopamine transporter; euphoria; gene targeting; genetically modified animals; human genetic material tag; human tissue; laboratory mouse; neuroanatomy; psychopharmacology; reinforcer

The rewarding/reinforcing effects of cocaine and amphetamines have been thought to be produced, at least in part, by blocking reuptake of dopamine by the dopamine transporter (DAT)and physiologically antagonizing the activities of the vesicular transporter VMAT2. DAT and VMAT2 are the sites that accumulate and sequester each of the dopamine selective toxins that produce the best current experimental models for Parkinsons disease. The DAT gene is expressed in dopaminergic neurons of the ventral midbrain, and serves as the only currently-available marker expressed almost exclusively by these cells, while VMAT2 is expressed in each monoaminergic sell group. During this year, we completed characterization of each of the human DAT gene exonic polymorphisms, and several intronic polymorphisms in several normal and disease. We have made substantial progreaa toward defining each of the polymorphisms in each of the VMAT2 exons in smaller groups of humans. Each protein displays two amino acid sequence variants; conservative in DAT and less conservative in VMAT2. Findings of continued strengthening of associations between the 3untranslated region VNTR marker and ADHD in several studies have bee completmented by initial findings that a VMAT2 polmorphism is differentially distributed among amphetamine preferring and amphetamine nonpreferring human research volunteers. interest in regulatory region polymorphisms at this interesting locus. - cocaine amphetamine Parkinson's diseasse ADHD - Human Subjects: Interview, Questionaires, or Surveys Only

可卡因和安非他明的奖赏/强化作用被认为至少部分是通过阻断多巴胺转运蛋白（DAT）对多巴胺的再摄取和生理拮抗囊泡转运蛋白VMAT 2的活性而产生的。DAT和VMAT 2是积累和隔离每种多巴胺选择性毒素的位点，这些毒素产生了目前最好的帕金森病实验模型。DAT基因在腹侧中脑的多巴胺能神经元中表达，并且作为几乎完全由这些细胞表达的唯一当前可用的标记物，而VMAT 2在每个单胺能sell组中表达。在这一年中，我们完成了每个人类DAT基因外显子多态性的表征，以及几个正常和疾病中的几个内含子多态性。我们已经在更小的人群中对每个VMAT 2外显子的多态性进行了大量的研究。每种蛋白质显示两种氨基酸序列变体; DAT中保守，VMAT 2中不太保守。在几项研究中，VMAT 2多态性在苯丙胺偏好和苯丙胺非偏好的人类研究志愿者中的分布差异，这一初步发现进一步证实了非翻译区VNTR标记物与ADHD之间的关联在持续加强。在这个有趣的基因座的调控区多态性的兴趣。- 注意力缺陷多动障碍-人类受试者：仅访谈、问卷调查或调查