title: Central PGE2 exhibits anxiolytic-like activity via EP1 and EP4 receptors in a manner dependent on serotonin 5-HT1A, dopamine D1 and GABAA receptors.
abstract: We found that centrally administered prostaglandin (PG) E(2) exhibited anxiolytic-like activity in the elevated plus-maze and open field test in mice. Agonists selective for EP(1) and EP(4) receptors, among four receptor subtypes for PGE(2), mimicked the anxiolytic-like activity of PGE(2). The anxiolytic-like activity of PGE(2) was blocked by an EP(1) or EP(4) antagonist, as well as in EP(4) but not EP(1) knockout mice. Central activation of either EP(1) or EP(4) receptors resulted in anxiolytic-like activity. The PGE(2)-induced anxiolytic-like activity was inhibited by antagonists for serotonin 5-HT(1A), dopamine D(1) and GABA(A) receptors. Taken together, PGE(2) exhibits anxiolytic-like activity via EP(1) and EP(4) receptors, with downstream involvement of 5-HT(1A), D(1) and GABA(A) receptor systems.
authors.affiliation: Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Gokasho Uji, Kyoto, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Suzuki
authors.forename: Chihiro
authors.initials: C
authors.lastname: Miyamoto
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Furuyashiki
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.forename: Kousaku
authors.initials: K
authors.lastname: Ohinata
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D015232:Dinoprostone / Q000494:pharmacology*; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009483:Neuropsychological Tests; D010879:Piperazines / Q000494:pharmacology; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology
chemical_list: D014151:Anti-Anxiety Agents; D001552:Benzazepines; D018757:GABA Modulators; D058787:GABA-A Receptor Antagonists; D010879:Piperazines; D017447:Receptors, Dopamine D1; D011963:Receptors, GABA-A; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; C534628:SCH 23390; D012702:Serotonin Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C081293:WAY 100135; D005442:Flumazenil; D015232:Dinoprostone; D001640:Bicuculline