神经科学
脉冲前抑制
多巴胺能
精神分裂症(面向对象编程)
谷氨酸的
心理学
前额叶皮质
医学
药理学
精神科
多巴胺
认知
受体
内科学
谷氨酸受体
作者
Els F. Halff,Grazia Rutigliano,Anna Garcia-Hidalgo,Oliver Howes
标识
DOI:10.1016/j.tins.2022.10.010
摘要
Schizophrenia remains a major health burden, highlighting the need for new treatment approaches. We consider the potential for targeting the trace amine (TA) system. We first review genetic, preclinical, and clinical evidence for the role of TAs in the aetiopathology of schizophrenia. We then consider how the localisation and function of the trace amine-associated receptor 1 (TAAR1) position it to modulate key brain circuits for the disorder. Studies in rodents using Taar1 knockout (TAAR1-KO) and overexpression models show that TAAR1 agonism inhibits midbrain dopaminergic and serotonergic activity, and enhances prefrontal glutamatergic function. TAAR1 agonists also reduce hyperactivity, attenuate prepulse inhibition (PPI) deficits and social withdrawal, and improve cognitive measures in animal models. Finally, we consider findings from clinical trials of TAAR1 agonists and how this approach may address psychotic and negative symptoms, tolerability issues, and other unmet needs in the treatment of schizophrenia.
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