Trace amine-associated receptor 1 modulates dopaminergic activity
Trace amine-associated receptor 1 modulates dopaminergic activity
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DOI：
10.1124/jpet.107.132647
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发表时间：
2008-03-01
影响因子：
3.5
通讯作者：
Hoener, Marius C.
中科院分区：
文献类型：
--
作者：
Lindemann, Lothar;Meyer, Claas Aiko;Hoener, Marius C.
最近发现的微量胺相关受体（TAAR）1提供了一个机会，分离微量胺对受体介导的多巴胺转运蛋白的影响。为了在生理水平上分离这两种效应，产生Taar 1敲除小鼠系。Taar 1基因敲除小鼠显示出对苯丙胺的敏感性增加，与野生型动物相比，苯丙胺引发的自发活动增加和纹状体多巴胺释放增加。在基线条件下，Taar 1基因敲除小鼠和野生型小鼠的运动和细胞外纹状体多巴胺水平相似。电生理记录显示Taar 1基因敲除小鼠腹侧被盖区多巴胺能神经元自发放电率升高。内源性TAAR 1激动剂p-酪胺特异性地降低了野生型但不是Taar 1敲除小鼠中这些神经元的尖峰频率，这与Taar 1在腹侧被盖区的显著表达一致。总之，数据揭示了TAAR 1作为多巴胺能神经传递的调节剂。
The recent identification of the trace amine-associated receptor (TAAR)1 provides an opportunity to dissociate the effects of trace amines on the dopamine transporter from receptor-mediated effects. To separate both effects on a physiological level, a Taar1 knockout mouse line was generated. Taar1 knockout mice display increased sensitivity to amphetamine as revealed by enhanced amphetamine-triggered increases in locomotor activity and augmented striatal release of dopamine compared with wild-type animals. Under baseline conditions, locomotion and extracellular striatal dopamine levels were similar between Taar1 knockout and wild-type mice. Electrophysiological recordings revealed an elevated spontaneous firing rate of dopaminergic neurons in the ventral tegmental area of Taar1 knockout mice. The endogenous TAAR1 agonist p-tyramine specifically decreased the spike frequency of these neurons in wild-type but not in Taar1 knockout mice, consistent with the prominent expression of Taar1 in the ventral tegmental area. Taken together, the data reveal TAAR1 as regulator of dopaminergic neurotransmission.