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 E₂ acts through EP1 to control impulsive behavior under stress, a finding potentially exploitable for development of drugs that attenuate impulsive behavior in humans.