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Pregnant albino rats administered VPA (500\u00a0mg\/kg, i.p.) or normal saline (10\u00a0mL\/kg, i.p.; vehicle\u2010control) on gestational day 12.5. The pups were given metformin (5, 50 or 500\u00a0mg\/kg, p.o.) or vehicle (10\u00a0mL\/kg, p.o.) daily from postnatal day (PND) 21\u201350. Social behaviour, spatial learning\/reference memory, repetitive behaviour and anxiety were assessed using the three\u2010chamber social assay, Morris water maze (MWM), Y maze and elevated plus maze tests (EPM), respectively. On PND 51, the animals were euthanized and brains removed for biochemical assay. In utero VPA exposure caused significant reduction in sociability index, social novelty preference index in three\u2010chambered apparatus and spatial learning and reference memory deficits in the MWM task as well as increase in repetitive\/anxiety\u2010like behaviour in Y maze and EPM tests, respectively, which were ameliorated by post\u2010treatment with metformin in a dose\u2010dependent manner. Moreover, prenatal VPA increased malondialdehyde (MDA) and nitrite levels as well as deficits in antioxidant enzymes activities in the hippocampus and prefrontal cortex (PFC) which were attenuated by metformin administration. Similarly, VPA\u2010induced increase in acetylcholinesterase activity in the hippocampus and PFC were attenuated by postnatal treatment with metformin. Findings from this study showed that postnatal administration of metformin prevented valproic acid\u2010induced autistic\u2010like behaviour. Hence, metformin could be a potential adjunct in the management of autism spectrum disorders.<\/jats:p>","DOI":"10.1111\/fcp.12567","type":"journal-article","created":{"date-parts":[[2020,5,16]],"date-time":"2020-05-16T09:12:28Z","timestamp":1589620348000},"page":"650-661","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Novel potential of metformin on valproic acid\u2010induced autism spectrum disorder in rats: involvement of antioxidant defence system"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9475-6754","authenticated-orcid":false,"given":"Ismail O.","family":"Ishola","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences College of Medicine, University of Lagos Idi\u2010Araba Lagos State Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aishat O.","family":"Balogun","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences College of Medicine, University of Lagos Idi\u2010Araba Lagos State Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olufunmilayo O.","family":"Adeyemi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences College of Medicine, University of Lagos Idi\u2010Araba Lagos State Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2013.12.001"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.6.861"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2017.04.017"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.2270"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2010.12.018"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2014.08.013"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/pcn.12602"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/aur.1967"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.12025SC"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2017.11.014"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.107975"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-012-0724-2"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2019.05.006"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13039"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00400"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2017.08.018"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4335"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2012.03.016"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2013.10.014"},{"key":"e_1_2_9_21_1","unstructured":"National Research Council.A guide for the care and use of laboratory animals. 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