Dipeptide Tyr-Leu Exhibits Anxiolytic-like Activity after Oral Administration via Activating Serotonin 5-HT_(1A),Dopamine D1 and GABA_A Receptors

摘要

We found that Tyr-Leu (YL), a simple dipeptide consisting of standard L-amino acids, dose-dependently exhibits potent anxiolytic-like activity (0.1-1 mg/kg, i.p., 0.3-3 mg/kg, p.o.) comparable to diazepam in the elevated plus-maze test. A retro-sequence peptide or a mixture of Tyr and Leu was inactive. The anxiolytic-like activity of YL was inhibited by antagonists for serotonin 5-HT_(1A), dopamine D1 and GABAa receptors; however, YL had no affinities for these receptors. We also determined that the order of their activations is 5-HT_(1A), D1 and GABAa receptors using selective agonists and antagonists. Taken together, YL may exhibit anxiolytic-like activity via activations of 5-HT_(1A) and D1 receptors followed by GABAa receptor.