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Speaker 1: Trace Amines are the type of chemical messenger found in low levels in the brain, as well as in peripheral tissues. They are structurally, and metabolically related to the classical monoamine neurotransmitters, dopamine, serotonin, and Norepinephrine, and contribute to neurotransmitter systems in the brain. Trace Amines bind to a family of G protein-coupled receptors called TAARs. The most well-studied being TAAR1.

TAAR1 is widely distributed throughout the brain, including in dopamine-rich regions, such as the VTA, and Substantial Nigra, Serotonin-rich regions, like the DRN as well as in the prefrontal cortex, hypothalamus, and amygdala, areas important to the pathophysiology of various neuropsychiatric disorders. Due to extremely low expression levels, determining the precise localization of TAAR1 within cells has been challenging. Initial studies provide evidence for both intercellular and membrane localization of TAAR1, with TAAR1, found both pre and postsynaptically.

Functionally, TAAR1 has been implicated in the modulation of dopaminergic, serotonergic, and glutamatergic circuitry in the brain. Studies show complex crosstalk exists between TAAR1 and these neurotransmitter systems. For example, TAAR1 activation can reduce dopamine neuron firing, while TAAR1 inhibition enhances it. Additionally, TAAR1 activation can inhibit serotonergic neuronal firing in the DRN, and modulate Glutamatergic activity in the prefrontal cortex. TAAR1's ability to regulate neurotransmitter signaling in brain systems important for mood, psychosis, reward processing, and cognition suggest CIS potential as a therapeutic target for several neuropsychiatric disorders.

Future research may not only help us to characterize viable therapeutic targets but also may lead to a better understanding of the pathophysiology of diseases in which neurotransmission is compromised.

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