title: Aromatic amino acid-leucine dipeptides exhibit anxiolytic-like activity in young mice.
abstract: We previously reported that Tyr-Leu (YL) exhibits potent anxiolytic-like activity comparable to diazepam in mice. In the current study, we revealed that aromatic amino acid-Leu, Phe-Leu and Trp-Leu (FL and WL, respectively), exhibited anxiolytic-like activity in the elevated plus-maze and open-field tests. FL and WL were orally active. Retro-sequence peptides of FL and WL were inactive. Similarly to YL, the anxiolytic-like activities of FL and WL were inhibited by WAY100135, SCH-23390 and bicuculline, antagonists of serotonin 5-HT1A, dopamine D1 and GABAA receptors, respectively, implying that FL and WL activate a common anxiolytic pathway to that of YL. Taken together, aromatic amino acid-Leu dipeptides such as YL, FL, and WL may exhibit anxiolytic-like activity in a manner dependent on the activation of 5-HT1A, D1 and GABAA receptors.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto 611-0011, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Mizushige
authors.forename: Norimasa
authors.initials: N
authors.lastname: Kanegawa
authors.forename: Ayako
authors.initials: A
authors.lastname: Yamada
authors.forename: Ami
authors.initials: A
authors.lastname: Ota
authors.forename: Ryuhei
authors.initials: R
authors.lastname: Kanamoto
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohinata
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D004151:Dipeptides / Q000494:pharmacology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D011869:Radioligand Assay; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D004151:Dipeptides; D017447:Receptors, Dopamine D1; D011963:Receptors, GABA-A; C509811:tryptophan-leucine; D044282:Receptor, Serotonin, 5-HT1A; C031703:tyrosylleucine