Trace amine-associated receptor 1 (TAAR1): Potential application in mood disorders: A systematic review

Abstract

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.

Keywords: Arousal; Attention; Bipolar disorder; Brain derived neurotrophic factor (BDNF); Cognitive control; Cognitive function; Depression; Mammalian target of rapamycin (mTOR); Medial prefrontal cortex (mPFC); Reward function; Trace amine-associated receptor 1 (TAAR1); Ventral tegmental area (VTA).