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The involvement of GABAergic neurotransmission, and especially a deficit of GABA<jats:sub>A<\/jats:sub> receptors that contain the \u03b15 subunits, were implicated in pathogenesis of ASD. Therefore, we tested MP\u2010III\u2010022, a positive allosteric modulator (PAM) selective for \u03b15GABAA receptors, in Wistar rats prenatally exposed to valproic acid, as an animal model useful for studying ASD. Postweaning rats of both sexes were treated for 7\u2009days with vehicle or MP\u2010III\u2010022 at two doses pharmacokinetically determined as selective, and thereafter tested in a behavioral battery (social interaction test, elevated plus maze, spontaneous locomotor activity, and standard and reverse Morris water maze). Additional rats were used for establishing a primary neuronal culture and performing calcium imaging, and determination of hippocampal mRNA levels of GABRA5, NKCC1, and KCC2. MP\u2010III\u2010022 prevented impairments in many parameters connected with social, repetitive and restrictive behavioral domains. The lower and higher dose was more effective in males and females, respectively. Intriguingly, MP\u2010III\u2010022 elicited certain changes in control animals similar to those manifested in valproate animals themselves. Behavioral results were mirrored in GABA switch and spontaneous neuronal activity, assessed with calcium imaging, and also in expression changes of three genes analyzed. Our data support a role of \u03b15GABAA receptors in pathophysiology of ASD, and suggest a potential application of selective PAMs in its treatment, that needs to be researched in a sex\u2010specific manner.<\/jats:p><\/jats:sec><jats:sec><jats:title>Lay Summary<\/jats:title><jats:p>In rats prenatally exposed to valproate as a model of autism, a modulator of \u03b15GABAA receptors ameliorated social, repetitive and restrictive impairments, and, intriguingly, elicited certain autism\u2010like changes in control rats. Behavioral results were mirrored in GABA switch and spontaneous neuronal activity, and partly in gene expression changes. This shows a role of \u03b15GABAA receptors in pathophysiology of ASD, and a potential application of their selective modulators in its treatment.<\/jats:p><\/jats:sec>","DOI":"10.1002\/aur.2699","type":"journal-article","created":{"date-parts":[[2022,3,10]],"date-time":"2022-03-10T12:07:46Z","timestamp":1646914066000},"page":"806-820","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Postweaning positive modulation of <scp>\u03b15GABAA<\/scp> receptors improves autism\u2010like features in prenatal valproate rat model in a sex\u2010specific manner"],"prefix":"10.1002","volume":"15","author":[{"given":"Anja","family":"Santra\u010d","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Belgrade \u2010 Faculty of Pharmacy  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dunja","family":"Bijeli\u0107","sequence":"additional","affiliation":[{"name":"Centre for Laser Microscopy, Institute of Physiology and Biochemistry \"Jean Giaja\" University of Belgrade \u2010 Faculty of Biology  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Stevanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Belgrade \u2010 Faculty of Pharmacy  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marija","family":"Bani\u0107evi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Belgrade \u2010 Faculty of Pharmacy  Belgrade Serbia"},{"name":"Institute of Pharmacy and Molecular Biotechnology, Bioinformatics and Functional Genomics Ruprecht\u2010Karls University Heidelberg  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovana","family":"Aran\u0111elovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Belgrade \u2010 Faculty of Pharmacy  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bojan","family":"Batini\u0107","sequence":"additional","affiliation":[{"name":"Department of Physiology University of Belgrade \u2010 Faculty of Pharmacy  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dishary","family":"Sharmin","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Wisconsin\u2010Milwaukee and the Milwaukee Institute of Drug Discovery  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James M.","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Wisconsin\u2010Milwaukee and the Milwaukee Institute of Drug Discovery  Milwaukee Wisconsin USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6934-9193","authenticated-orcid":false,"given":"Miroslav M.","family":"Savi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Belgrade \u2010 Faculty of Pharmacy  Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,3,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"crossref","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and statistical manual of mental disorders","author":"American Psychiatric Association (APA)","year":"2013"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.59.4.814"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.06.015"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1001081"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2015.11.025"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijdevneu.2017.06.001"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2018.05.014"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep39969"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1013238809666"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2013.03.030"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamapediatrics.2014.210"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13229-018-0221-9"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0307231101"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(87)90105-3"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000509109"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","unstructured":"Chen Y.\u2010W. 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