title: Prostaglandin E receptor EP1 controls impulsive behavior under stress.
abstract: Animals under stress take adaptive actions that may lead to various types of behavioral disinhibition. Such behavioral disinhibition, when expressed excessively and impulsively, can result in harm in individuals and cause a problem in our society. We now show that, under social or environmental stress, mice deficient in prostaglandin E receptor subtype EP1 (Ptger1(-/-)) manifest behavioral disinhibition, including impulsive aggression with defective social interaction, impaired cliff avoidance, and an exaggerated acoustic startle response. This phenotype was reproduced in wild-type mice by administration of an EP1-selective antagonist, whereas administration of an EP1-selective agonist suppressed electric-shock-induced impulsive aggression. Dopamine turnover in the frontal cortex and striatum was increased in Ptger1(-/-) mice, and administration of dopaminergic antagonists corrected their behavioral phenotype. These results suggest that prostaglandin E(2) acts through EP1 to control impulsive behavior under stress, a finding potentially exploitable for development of drugs that attenuate impulsive behavior in humans.
authors.affiliation: Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Matsuoka
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Furuyashiki
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.forename: Taku
authors.initials: T
authors.lastname: Nagai
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Bito
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Shiho
authors.initials: S
authors.lastname: Kitaoka
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ushikubi
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism; D015232:Dinoprostone / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D007175:Impulsive Behavior; D007266:Inhibition, Psychological; D051379:Mice; D018345:Mice, Knockout; D018078:Receptors, Prostaglandin E / Q000502:physiology*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013312:Stress, Physiological / Q000523:psychology*
chemical_list: C545635:PTGER1 protein, human; C545636:Ptger1 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D015232:Dinoprostone; D004298:Dopamine