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

可卡因和安非他明的奖励/强化作用被认为至少在一定程度上是通过阻断多巴胺转运体（DAT）对多巴胺的再摄取和从生理上拮抗囊泡转运体VMAT2的活性而产生的。DAT和VMAT2是积累和隔离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基因在中脑腹侧多巴胺能神经元中表达，并且是目前唯一可用的几乎完全由这些细胞表达的标记物，而VMAT2在每个单胺能出售组中表达。在这一年里，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的内含子多态性。我们已经在确定较小人群中每个VMAT2外显子的多态性方面取得了实质性进展。每个蛋白质显示两个氨基酸序列变异；在DAT中保守，在VMAT2中不那么保守。在几项研究中，VMAT2多态性在安非他明偏好和非安非他明偏好的人类研究志愿者中存在差异分布，这一初步发现补充了3非翻译区VNTR标记与ADHD之间持续加强的关联。对这个有趣位点的调控区多态性感兴趣。-可卡因安非他明帕金森病ADHD -人类受试者：访谈，问卷调查或仅调查

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