TAAR1 agonist reduces α-NETA induced dyskinesia

As of today, sufficient evidence has been collected regarding the role of trace amines (TAs) as neuromodulators in the mammalian central nervous system. TAs share structural similarities with classical biogenic amines, while the changes in their concentration have been linked to various mental disorders. Two widely expressed members of the TAs receptor family in the human central nervous system are TAAR1 and TAAR5 receptors. The first part of this research investigates the behavioral effects of α-NETA injection (2-(alpha-naphthoyl) ethyltrimethylammonium iodide, 10 mg/kg, IP) on both TAAR5 knockout (KO TAAR5) and wild-type (WT) mice. The second part examines the impact of the TAAR1 agonist, RO 5263397, on dyskinesia induced by α-NETA injection in C57BL/6 male mice. The α-NETA (10 mg/kg) injection causes dyskinesia both in wild-type and KO TAAR5 mice, suggesting that α-NETA-induced dyskinesia is unrelated to the effects on TAAR5 receptors. The second part of the study found that preliminary administration of a high dose (1 mg/kg) of a TAAR1 agonist inhibited α-NETA-induced dyskinesia 90 min after injection. In addition, the number of expanded dyskinesias was significantly reduced in groups pre-injected with TAAR1 agonist. These findings suggest that TAAR1 agonists hold promise for the treatment of certain forms of dyskinesia.