TRACE AMINE-ASSOCIATED RECEPTOR 1 IS A MODULATOR OF BRAIN MONOAMINERGIC SYSTEMS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. As human and rodent trace amine receptors diverge in structure, subtype number and brain distribution, we postulate that non-human primates will provide a more suitable model for uncovering the physiological and pharmacological relevance of trace amine subtypes. In this regard, there is a 96 percent sequence identity for Trace Amine Associated Receptor 1 (TAAR1) in non-human primate and human. To establish fundamental information needed to explore TAAR subtype function, we investigate non-human primate TAAR subtype structure, pharmacology, signal transduction and brain distribution. We utilize luciferase assays sensitive to different signal transduction pathways to uncover agonists as well as antagonists that block agonist-induced receptor activation. We map TAAR subtype mRNA and protein distribution in primate brain using real-time RT-PCR and immunohistochemistry, to discern which receptor subtypes are expressed in brain. We study genetic variation at this locus, to assess whether polymorphisms may be implicated in addiction and other psychiatric disorders. Our studies form the basis for investigating the physiological and pharmacological relevance of trace amine receptors in a primate model, and provide novel leads for developing therapeutic agents to treat addiction and neuropsychiatric disorders.