Prostaglandin E receptor EP1 controls impulsive behavior under stress.
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.
Matsuoka
Yoko
Y
Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan.
Furuyashiki
Tomoyuki
T
Yamada
Kiyofumi
K
Nagai
Taku
T
Bito
Haruhiko
H
Tanaka
Yasuhiro
Y
Kitaoka
Shiho
S
Ushikubi
Fumitaka
F
Nabeshima
Toshitaka
T
Narumiya
Shuh
S
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*
C545635:PTGER1 protein, human; C545636:Ptger1 protein, mouse; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D015232:Dinoprostone; D004298:Dopamine