Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada.
Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, Ontario, Canada; Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada.
Neurosci Biobehav Rev. 2021 Dec;131:192-210. doi: 10.1016/j.neubiorev.2021.09.020. Epub 2021 Sep 16.
There is a need for innovation with respect to therapeutics in psychiatry. Available evidence indicates that the trace amine-associated receptor 1 (TAAR1) agonist SEP-363856 is promising, as it improves measures of cognitive and reward function in schizophrenia. Hedonic and cognitive impairments are transdiagnostic and constitute major burdens in mood disorders. Herein, we systematically review the behavioural and genetic literature documenting the role of TAAR1 in reward and cognitive function, and propose a mechanistic model of TAAR1's functions in the brain. Notably, TAAR1 activity confers antidepressant-like effects, enhances attention and response inhibition, and reduces compulsive reward seeking without impairing normal function. Further characterization of the responsible mechanisms suggests ion-homeostatic, metabolic, neurotrophic, and anti-inflammatory enhancements in the limbic system. Multiple lines of evidence establish the viability of TAAR1 as a biological target for the treatment of mood disorders. Furthermore, the evidence suggests a role for TAAR1 in reward and cognitive function, which is attributed to a cascade of events that are relevant to the cellular integrity and function of the central nervous system.
在精神病学的治疗方法上需要创新。现有证据表明，痕量胺相关受体 1（TAAR1）激动剂 SEP-363856 很有前途，因为它可以改善精神分裂症的认知和奖励功能。快感和认知障碍具有跨诊断性，是情绪障碍的主要负担。在此，我们系统地回顾了记录 TAAR1 在奖励和认知功能中的作用的行为和遗传文献，并提出了 TAAR1 在大脑中的功能的机制模型。值得注意的是，TAAR1 活性赋予抗抑郁样作用，增强注意力和反应抑制，并减少强迫性奖励寻求而不损害正常功能。对负责机制的进一步特征描述表明，在边缘系统中增强了离子稳态、代谢、神经营养和抗炎作用。多条证据证实 TAAR1 作为治疗情绪障碍的生物靶标具有可行性。此外，有证据表明 TAAR1 在奖励和认知功能中发挥作用，这归因于与中枢神经系统的细胞完整性和功能相关的一系列事件。
