Loss of autoreceptor functions in mice lacking the dopamine transporter
Loss of autoreceptor functions in mice lacking the dopamine transporter
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DOI：
10.1038/10204
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发表时间：
1999-07-01
影响因子：
25
通讯作者：
Caron, MG
中科院分区：
文献类型：
--
作者：
Jones, SR;Gainetdinov, RR;Caron, MG
自受体通过改变神经元功能以响应细胞外多巴胺水平的变化，为多巴胺神经元提供了重要的抑制反馈机制。多巴胺升高可能是几种神经精神疾病的一个组成部分。然而，在这种情况下，有关自受体状态的证据仍然难以捉摸。在缺乏多巴胺转运体（DAT）的小鼠中评估多巴胺自受体的功能。小鼠中DAT基因的遗传缺失导致细胞外多巴胺水平的持续升高。对这些小鼠的冲动、合成和释放调节自身受体的直接评估显示，它们几乎完全丧失了功能。这些发现可能为了解高多巴胺能的神经化学后果提供见解。
Autoreceptors provide an important inhibitory feedback mechanism for dopamine neurons by altering neuronal functions in response to changes in extracellular levels of dopamine. Elevated dopamine may be a component of several neuropsychiatric disorders. However, evidence concerning the state of autoreceptors in such conditions has remained elusive. The function of dopamine autoreceptors was assessed in mice lacking the dopamine transporter (DAT). Genetic deletion of the DAT gene in mice results in a persistent elevation in levels of extracellular dopamine. Direct assessment of impulse-, synthesis- and release-regulating autoreceptors in these mice reveals a nearly complete loss of function. These findings may provide insight into the neurochemical consequences of hyperdopaminergia.