Trace amines, a group of amines expressed at the nanomolar level in the mammalian brain, can modulate monoamine transmission. The discovery of and the functional research on the trace amine-associated receptors (TAARs), especially the most well-characterized TAAR1, have largely facilitated our understanding of the function of the trace amine system in the brain. TAAR1 is expressed in the mammalian brain at a low level and widely distributed in the monoaminergic system, including the ventral tegmental area and substantial nigra, where the dopamine neurons reside in the mammalian brain. Growing in vitro and in vivo evidence has demonstrated that TAAR1 could negatively modulate monoamine transmission and play a crucial role in many psychiatric disorders, including schizophrenia, substance use disorders, sleep disorders, depression, and anxiety. Notably, in the last two decades, many studies have repeatedly confirmed the pharmacological effects of the selective TAAR1 ligands in various preclinical models of psychiatric disorders. Recent clinical trials of the dual TAAR1 and serotonin receptor agonist ulotaront also revealed a potential efficacy for treating schizophrenia. Here, we review the current understanding of the TAAR1 system and the recent advances in the elucidation of behavioral and physiological properties of TAAR1 agonists evaluated both in preclinical animal models and clinical trials. We also discuss the potential TAAR1-dependent signaling pathways and the cellular mechanisms underlying the inhibitory effects of TAAR1 activation on drug addiction. We conclude that TAAR1 is an emerging target for the treatment of psychiatric disorders.

痕量胺是哺乳动物大脑中以纳摩尔水平表达的一组胺，可以调节单胺传输。微量胺相关受体（TAAR）的发现和功能研究，尤其是最明确的TAAR1，在很大程度上促进了我们对大脑中微量胺系统功能的理解。TAAR1在哺乳动物大脑中低水平表达，并广泛分布于单胺能系统，包括腹侧被盖区和实质黑质，多巴胺神经元位于哺乳动物大脑中。越来越多的体外和体内证据表明，TAAR1 可以负向调节单胺传递，并在许多精神疾病中发挥至关重要的作用，包括精神分裂症、药物滥用障碍、睡眠障碍、抑郁症和焦虑症。值得注意的是，在过去的二十年里，许多研究反复证实了选择性TAAR1配体在各种精神疾病临床前模型中的药理作用。最近的 TAAR1 和血清素受体激动剂 ulotaront 双重临床试验也揭示了治疗精神分裂症的潜在功效。在这里，我们回顾了目前对 TAAR1 系统的理解，以及在临床前动物模型和临床试验中评估的 TAAR1 激动剂的行为和生理特性的阐明的最新进展。我们还讨论了潜在的 TAAR1 依赖性信号通路以及 TAAR1 激活对药物成瘾的抑制作用的细胞机制。我们的结论是 TAAR1 是治疗精神疾病的新兴靶点。