Abstract

We found that Tyr-Leu (YL) dose-dependently exhibits potent anxiolytic-like activity (0.1–1mg/kg, i.p.) comparable to diazepam in the elevated plus-maze test in mice. YL was orally active (0.3–3mg/kg). 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-HT1A, dopamine D1 and GABAA receptors; however, YL had no affinity for them. We also determined the order of their activation is 5-HT1A, D1 and GABAA receptors using selective agonists and antagonists. Taken together, YL may exhibit anxiolytic-like activity via activation of 5-HT1A, D1 and GABAA receptors.

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