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In this pilot study, we examined effects of prenatal exposure to a moderate dose of VPA on behavior and on transcriptomic expression in three brain regions that mediate social behavior. Pregnant Long Evans rats were injected with 350 mg\/kg VPA or saline on gestational day 13. A modified social interaction test was used to assess social behavior and social preference\/avoidance during early and late adolescence and in adulthood. VPA\u2010exposed animals demonstrated more social investigation and play fighting than control animals. Social investigation, play fighting, and contact behavior also differed as a function of age; the frequency of these behaviors increased in late adolescence. Social preference and locomotor activity under social circumstances were unaffected by treatment or age. Thus, a moderate prenatal dose of VPA produces behavioral alterations that are substantially different from the outcomes that occur following exposure to a higher dose. At adulthood, VPA\u2010exposed subjects exhibited transcriptomic abnormalities in three brain regions: anterior amygdala, cerebellar vermis, and orbitofrontal cortex. A common feature among the proteins encoded by the dysregulated genes was their ability to be modulated by acetylation. Analysis of the expression of individual exons also revealed that genes involved in post\u2010translational modification and epigenetic regulation had particular isoforms that were ubiquitously dysregulated across brain regions. The vulnerability of these genes to the epigenetic effects of VPA may highlight potential mechanisms by which prenatal VPA exposure alters the development of social behavior.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2013.09.002","type":"journal-article","created":{"date-parts":[[2013,9,19]],"date-time":"2013-09-19T04:48:31Z","timestamp":1379566111000},"page":"740-750","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Acute prenatal exposure to a moderate dose of valproic acid increases social behavior and alters gene expression in rats"],"prefix":"10.1002","volume":"31","author":[{"given":"Ori S.","family":"Cohen","sequence":"first","affiliation":[{"name":"Psychiatric Genetic Epidemiology &amp; Neurobiology Laboratory (PsychGENe Lab) Department of Psychiatry and Behavioral Sciences SUNY Upstate Medical University Syracuse NY 13210 United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena I.","family":"Varlinskaya","sequence":"additional","affiliation":[{"name":"Department of Psychology Center for Development and Behavioral Neuroscience Binghamton University Binghamton NY 13902 United States"},{"name":"Developmental Exposure Alcohol Research Center Baltimore MD 21201 United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carey A.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Psychiatric Genetic Epidemiology &amp; Neurobiology Laboratory (PsychGENe Lab) Department of Psychiatry and Behavioral Sciences SUNY Upstate Medical University Syracuse NY 13210 United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen J.","family":"Glatt","sequence":"additional","affiliation":[{"name":"Psychiatric Genetic Epidemiology &amp; Neurobiology Laboratory (PsychGENe Lab) Department of Psychiatry and Behavioral Sciences SUNY Upstate Medical University Syracuse NY 13210 United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra M.","family":"Mooney","sequence":"additional","affiliation":[{"name":"Developmental Exposure Alcohol Research Center Baltimore MD 21201 United States"},{"name":"Developmental Exposure Alcohol Research Center Binghamton NY 13902 United States"},{"name":"Developmental Exposure Alcohol Research Center Cortland NY 13054 United States"},{"name":"Developmental Exposure Alcohol Research Center Syracuse NY 13210 United States"},{"name":"Department of Pediatrics University of Maryland School of Medicine Baltimore MD 21201 United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,9,19]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901940102"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901940103"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.901940411"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cm.20296"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(96)80048-7"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80054-9"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.09-133587"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2004.12.003"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(02)00223-1"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0893-133X(99)00026-3"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2012.09.005"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2003-4-5-p3"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303740200"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1037\/0735-7044.118.2.298"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.090491897"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2009.12.054"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1978.tb07001.x"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(03)01273-1"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81416-6"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.2174\/1875692110907030164"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2010.01075.x"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2010.02.057"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0705003104"},{"key":"e_1_2_9_25_1","first-page":"255","article-title":"Deletion at chromosome 16p13.3 as a cause of Rubinstein\u2013Taybi syndrome: clinical aspects","volume":"52","author":"Hennekam R.C.","year":"1993","journal-title":"Am. 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