Trace amine-associated receptor 1 (TAAR1) senses endogenous amine-containing metabolites (EAMs) and is involved in mediating diverse psychological functions [1]. It is expressed in the mammalian brain, especially within the monoaminergic systems, and can modulate monoamine transmission, including dopamine transmission in the mesocorticolimbic system [2,3,4,5]. TAAR1 activation is beneficial for schizophrenia treatment without catalepsy side-effects, and it may also play a role in modulating psychostimulant addiction [1,2].

Studies in Taar1 knockout (TAAR1-KO) rodent models show that TAAR1 agonism inhibits midbrain dopaminergic and serotonergic activity, and enhances prefrontal glutamatergic function [3]. In general, activation of TAAR1 attenuated while knockout of TAAR1 potentiated psychostimulant abuse-related behaviors [2].

In conclusion, TAAR1 is crucial for modulating monoaminergic and glutamatergic neurotransmission, which is significant for psychological functions. The use of TAAR1-KO mouse models has revealed its role in schizophrenia and psychostimulant addiction, suggesting that TAAR1 agonists could be promising for treating these disorders.

References:

1. Shang, Pan, Rong, Naikang, Jiang, Jing-Jing, Yang, Fan, Sun, Jin-Peng. 2023. Structural and signaling mechanisms of TAAR1 enabled preferential agonist design. In Cell, 186, 5347-5362.e24. doi:10.1016/j.cell.2023.10.014. https://pubmed.ncbi.nlm.nih.gov/37963465/

2. Liu, Jianfeng, Wu, Ruyan, Li, Jun-Xu. 2020. TAAR1 and Psychostimulant Addiction. In Cellular and molecular neurobiology, 40, 229-238. doi:10.1007/s10571-020-00792-8. https://pubmed.ncbi.nlm.nih.gov/31974906/

3. Halff, Els F, Rutigliano, Grazia, Garcia-Hidalgo, Anna, Howes, Oliver D. 2022. Trace amine-associated receptor 1 (TAAR1) agonism as a new treatment strategy for schizophrenia and related disorders. In Trends in neurosciences, 46, 60-74. doi:10.1016/j.tins.2022.10.010. https://pubmed.ncbi.nlm.nih.gov/36369028/

4. Liu, Jianfeng, Wu, Ruyan, Li, Jun-Xu. 2023. TAAR1 as an emerging target for the treatment of psychiatric disorders. In Pharmacology & therapeutics, 253, 108580. doi:10.1016/j.pharmthera.2023.108580. https://pubmed.ncbi.nlm.nih.gov/38142862/

5. Liu, Jian-Feng, Li, Jun-Xu. 2018. TAAR1 in Addiction: Looking Beyond the Tip of the Iceberg. In Frontiers in pharmacology, 9, 279. doi:10.3389/fphar.2018.00279. https://pubmed.ncbi.nlm.nih.gov/29636691/