TAAR1 and Psychostimulant Addiction.
TAAR1 and Psychostimulant Addiction.
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DOI：
10.1007/s10571-020-00792-8
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发表时间：
2020-03
影响因子：
4
通讯作者：
Li JX
中科院分区：
文献类型：
--
作者：
Liu J;Wu R;Li JX
痕量胺相关受体1是痕量胺的最佳表征受体之一。越来越多的证据表明，TAAR1负调节单胺能活性，包括多巴胺在中皮质边缘系统的传输。神经化学分析表明，选择性TAAR1完全和部分激动剂是有效的，以防止精神兴奋剂诱导的多巴胺在体外和体内传输。在过去的几十年里，许多精神兴奋剂成瘾的临床前模型，如药物诱导的行为敏化，药物诱导的条件性位置偏爱，药物自我给药，药物辨别和复发模型被用来评估TAAR 1激动剂对精神兴奋剂作用的影响。总的来说，TAAR1的激活减弱，而TAAR1的敲除增强了精神兴奋剂相关的滥用行为。本文就TAAR 1及其激动剂在调节精神兴奋剂成瘾中的研究进展作一综述。我们讨论了TAAR 1完全和部分激动剂的神经化学和行为效应之间的相似性和差异。我们还讨论了几个问题，包括滥用倾向，睡眠减少，物种依赖性的影响，可能会影响TAAR 1激动剂从临床前研究到临床应用的成功翻译。总之，尽管需要进一步的研究来解决一些问题和潜在的神经机制，但TAAR 1激动剂是一类有前途的药物疗法，用于治疗精神兴奋剂成瘾和预防复发。
Trace amine-associated receptor 1 is one of the best-characterized receptors of trace amines. Growing evidence shows that TAAR1 negatively regulates the monoaminergic activity, including dopamine transmission in the mesocorticolimbic system. Neural chemical assays demonstrated that selective TAAR1 full and partial agonists were effective to prevent psychostimulants-induced dopamine transmission in vitro and in vivo. In the last decades, many preclinical models of psychostimulant addiction such as drug-induced behavioral sensitization, drug-induced conditioned place preference, drug self-administration, drug discrimination, and relapse models were used to assess the effects of TAAR1 agonists on psychostimulants’ actions. In general, activation of TAAR1 attenuated while knockout of TAAR1 potentiated psychostimulants-associated behaviors of abuse. Here we review the advances in TAAR1 and its agonists in modulating psychostimulant addiction. We discuss the similarities and differences between the neural chemical and behavioral effects of TAAR1 full and partial agonists. We also discuss several concerns including abuse liability, sleep reduction, and species-dependent effects that might affect successful translation of TAAR1 agonists from preclinical studies to clinical application. In conclusion, although further investigations are in need to address some concerns and the underlying neural mechanisms, TAAR1 agonists are a class of promising pharmacotherapy to treat psychostimulant addiction and prevent relapse.
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