Trace amine-associated receptors (TAARs) family belongs to a vast group of G-protein coupled receptors. TAAR1, the most well-known member of this family, with expression in various brain regions is a potential therapeutic target for schizophrenia. On the other hand, the remaining TAARs are primarily found in the olfactory epithelium and are considered a novel type of olfactory receptors. Nevertheless, there is evidence that other TAARs may have a function in both the CNS and periphery. Here using various approaches, we studied TAAR9 receptor. Standard behavioral tests were conducted on rats with a CRISPR/Cas9 TAAR9 gene knockout, including the Open field, Elevated plus maze, T-test, Stress-induced hyperthermia, and Porsolt Test. The results showed no significant changes in most behavioral tests, except for a lower stress-induced hyperthermia in the knockout rats. To further investigate thermoregulation, iButton sensors were implanted to monitor core temperature, which was found to be higher in the TAAR9-KO rats. Additionally, HPLC-ED analysis revealed an increased level of dopamine in the hypothalamus. RT-PCR was used to assess TAAR9 expression in the brain, which was found in the midbrain (substantia nigra and VTA), hypothalamus, and medulla oblongata. The study also attempted to identify TAAR9 ligands by optimizing TAAR9 expression in eukaryotic HEK293T cells and screening 400 compounds for their ability to activate Gαs-dependent signaling pathways. A few previously known TAAR9 ligands, such as N-methylpiperidine and cadaverine, were confirmed. In this study with TAAR9 gene knockout model we for the first time show TAAR9 expression in the brain and its possible role in thermoregulation. However, more research is needed to fully understand the functional role of TAAR9 in both the brain and periphery. The authors thank St. Petersburg State Vivarium for assistance with animal studies.
This work was supported by the project ID:94030300 of the St. Petersburg State University, St.Petersburg, Russia.