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This suggests that reduced prefrontal dopaminergic activity is associated with behavioral abnormalities in VPA\u2010treated mice. In the present study, we examined whether the attention deficit\/hyperactivity disorder drugs methylphenidate and atomoxetine (which increase dopamine release in the prefrontal cortex, but not striatum, in mice) could alleviate the behavioral abnormalities and changes in dendritic spine morphology induced by prenatal VPA exposure. We found that methylphenidate and atomoxetine increased prefrontal dopamine and noradrenaline release in VPA\u2010treated mice. Acute treatment with methylphenidate or atomoxetine did not alleviate the social interaction deficits or recognition memory impairment in VPA\u2010treated mice, while chronic treatment for 2 weeks did. Methylphenidate or atomoxetine for 2 weeks also improved the prenatal VPA\u2010induced decrease in dendritic spine density in the prefrontal cortex. The effects of these drugs on behaviors and dendritic spine morphology were antagonized by concomitant treatment with the dopamine\u2010D<jats:sub>1<\/jats:sub> receptor antagonist SCH39166 or the dopamine\u2010D<jats:sub>2<\/jats:sub> receptor antagonist raclopride, but not by the \u03b1<jats:sub>2<\/jats:sub>\u2010adrenoceptor antagonist idazoxan. These findings suggest that chronic treatment with methylphenidate or atomoxetine improves abnormal behaviors and diminishes the reduction in spine density in VPA\u2010treated mice via a prefrontal dopaminergic system\u2010dependent mechanism. <jats:bold><jats:italic>Autism Res<\/jats:italic><\/jats:bold> <jats:italic>2016, 9: 926\u2013939<\/jats:italic>. \u00a9 2015 International Society for Autism Research, Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/aur.1596","type":"journal-article","created":{"date-parts":[[2015,12,30]],"date-time":"2015-12-30T13:25:07Z","timestamp":1451481907000},"page":"926-939","source":"Crossref","is-referenced-by-count":54,"title":["Improvement by methylphenidate and atomoxetine of social interaction deficits and recognition memory impairment in a mouse model of valproic acid\u2010induced autism"],"prefix":"10.1002","volume":"9","author":[{"given":"Yuta","family":"Hara","sequence":"first","affiliation":[{"name":"Laboratory of Medicinal Pharmacology, 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