{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T18:25:20Z","timestamp":1790533520095,"version":"4.1.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T00:00:00Z","timestamp":1661126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:p>Disrupted processing of social cues and altered social behaviors are among the core symptoms of autism spectrum disorders (ASDs), and they emerge as early as the first year of life. These differences in sensory abilities may affect the ability of children with ASDs to securely attach to a caregiver and experience caregiver buffering of stress. Prenatal exposure to valproic acid (VPA) has been used to model some aspects of ASDs in rodents. Here, we asked whether prenatal VPA exposure altered infant rats\u2019 behavioral responsivity to maternal olfactory cues in an Odor Preference Test (OPT) and affected maternal buffering of infants\u2019 stress responsivity to shock. In the odor preference test, 1-week old rats treated with VPA during pregnancy appeared to have impaired social recognition and\/or may be less motivated to approach social odors in early infancy. These effects were particularly prominent in female pups. In 2-week old rats, VPA-exposed pups and saline-exposed pups showed similar preferences for home cage bedding. Although VPA-exposed pups may initially have a deficit in this attachment-related behavior they do recover typical responses to home cage bedding in later infancy. Both control and VPA-exposed pups showed robust stress hormone responses to repeated shocks, an effect which was blocked when a calm mother was present during shock exposure. No sex differences in the effect of maternal presence on the stress response to shock and no interactions between sex and prenatal drug exposure were observed. Although VPA-exposed pups may show impaired responsivity to maternal cues in early infancy, maternal presence is still capable of regulating the stress response in VPA-exposed pups. In this study we demonstrate the importance of utilizing multiple batteries of tests in assessing behavior, dissecting the behavior on one test into different components. Our results inform about the underlying behavioral characteristics of some of the ASD phenotypes, including sex differences reported by clinical studies, and could shed light on potential opportunities for intervention.<\/jats:p>","DOI":"10.3389\/fnbeh.2022.959485","type":"journal-article","created":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T05:32:56Z","timestamp":1661146376000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Intact maternal buffering of stress response in infant rats despite altered responsivity towards maternal olfactory cues in the valproic acid model of autism-like behavior"],"prefix":"10.3389","volume":"16","author":[{"given":"Amanda M.","family":"White","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xianli","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Debiec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,8,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.mcn.2014.01.007","article-title":"Increased BDNF expression in fetal brain in the valproic acid model of autism","volume":"59","author":"Almeida","year":"2014","journal-title":"Mol. Cell. Neurosci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1016\/0003-3472(75)90114-1","article-title":"Postnatal development of locomotion in the laboratory rat","volume":"23","author":"Altman","year":"1975","journal-title":"Anim. Behav."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.ss6706a1","article-title":"Prevalence of autism spectrum disorder among children aged 8 years - Autism and developmental disabilities monitoring network, 11 Sites, United States, 2014","volume":"67","author":"Baio","year":"2018","journal-title":"MMWR Surveill. Summ."},{"key":"B4","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s13229-017-0160-x","article-title":"Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally","volume":"8","author":"Barrett","year":"2017","journal-title":"Mol. Autism"},{"key":"B5","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/0003-3472(64)90062-4","article-title":"The ontogeny of behaviour in the albino rat","volume":"12","author":"Bolles","year":"1964","journal-title":"Anim. Behav."},{"key":"B6","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/s40473-017","article-title":"Enduring neural and behavioral effects of early life adversity in infancy: consequences of maternal abuse and neglect, trauma and fear","volume":"4","author":"Boulanger-Bertolus","year":"2017","journal-title":"Curr. Behav. Neurosci. Rep."},{"key":"B7","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1192\/bjp.130.3.201","article-title":"The making and breaking of affectional bonds: I aetiology and psychopathology in the light of attachment theory","volume":"130","author":"Bowlby","year":"1977","journal-title":"Br. J. Psychiatry"},{"key":"B8","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1037\/0735-7036.108.3.298","article-title":"Hypothermic vocalizations of rat pups (Rattus norvegicus) elicit and direct maternal search behavior","volume":"108","author":"Brunelli","year":"1994","journal-title":"J. Comp. Psychol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"1696","DOI":"10.1001\/jama.2013.2270","article-title":"Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism","volume":"309","author":"Christensen","year":"2013","journal-title":"JAMA"},{"key":"B10","doi-asserted-by":"publisher","first-page":"12222","DOI":"10.1073\/pnas.1316740111","article-title":"Intergenerational transmission of emotional trauma through amygdala-dependent mother-to-infant transfer of specific fear","volume":"111","author":"Debiec","year":"2014","journal-title":"Proc. Natl. Acad. Sci. U S A"},{"key":"B11","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1016\/j.nlm.2016.10.015","article-title":"The neurobiology of safety and threat learning in infancy","volume":"143","author":"Debiec","year":"2017","journal-title":"Neurobiol. Learn. Mem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1254","DOI":"10.1016\/j.neubiorev.2010.12.013","article-title":"Fetal exposure to teratogens: evidence of genes involved in autism","volume":"35","author":"Dufour-Rainfray","year":"2011","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B13","doi-asserted-by":"publisher","first-page":"424","DOI":"10.3389\/fnins.2016.00424","article-title":"Does prenatal valproate interact with a genetic reduction in the serotonin transporter? A rat study on anxiety and cognition","volume":"10","author":"Ellenbroek","year":"2016","journal-title":"Front. Neurosci."},{"key":"B14","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s11920-018-0874-2","article-title":"Sex differences in autism spectrum disorder: a review","volume":"20","author":"Ferri","year":"2018","journal-title":"Curr. Psychiatry Rep."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1111\/jcpp.12728","article-title":"Randomised trial of a parent-mediated intervention for infants at high risk for autism: longitudinal outcomes to age 3 years","volume":"58","author":"Green","year":"2017","journal-title":"J. Child Psychol. Psychiatry"},{"key":"B16","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1177\/1745691616680612","article-title":"Social buffering of stress in development: a career perspective","volume":"12","author":"Gunnar","year":"2017","journal-title":"Perspect. Psychol. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1002\/dev.420110513","article-title":"Ultrasonic vocalization during social interaction and isolation in 2-week-old rats","volume":"11","author":"Hofer","year":"1978","journal-title":"Dev. Psychobiol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1597","DOI":"10.1037\/dev0000029","article-title":"Early social deprivation and the social buffering of cortisol stress responses in late childhood: an experimental study","volume":"51","author":"Hostinar","year":"2015","journal-title":"Dev. Psychol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1017\/S1461145711001714","article-title":"Autism-like behaviours with transient histone hyperacetylation in mice treated prenatally with valproic acid","volume":"16","author":"Kataoka","year":"2013","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1007\/s12035-013-8535-2","article-title":"Pax6-dependent cortical glutamatergic neuronal differentiation regulates autism-like behavior in prenatally valproic acid-exposed rat offspring","volume":"49","author":"Kim","year":"2014","journal-title":"Mol. Neurobiol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.neulet.2014.03.066","article-title":"Valproic acid selectively suppresses the formation of inhibitory synapses in cultured cortical neurons","volume":"569","author":"Kumamaru","year":"2014","journal-title":"Neurosci. Lett."},{"key":"B22","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.brainres.2017.06.018","article-title":"Reduced protein expressions of cytomembrane GABA(A)R\u03b23 at different postnatal developmental stages of rats exposed prenatally to valproic acid","volume":"1671","author":"Li","year":"2017","journal-title":"Brain Res."},{"key":"B23","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/S0140-6736(18)31129-2","article-title":"Autism spectrum disorder","volume":"392","author":"Lord","year":"2018","journal-title":"Lancet"},{"key":"B24","doi-asserted-by":"publisher","first-page":"901","DOI":"10.1038\/sj.npp.1301453","article-title":"Abnormal fear conditioning and amygdala processing in an animal model of autism","volume":"33","author":"Markram","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1002\/dev.21102","article-title":"Odor-induced crawling locomotion in the newborn rat: effects of amniotic fluid and milk","volume":"56","author":"Mendez-Gallardo","year":"2014","journal-title":"Dev. Psychobiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1016\/j.bbr.2013.09.049","article-title":"Inhibition of histone deacetylase in utero causes sociability deficits in postnatal mice","volume":"257","author":"Moldrich","year":"2013","journal-title":"Behav. Brain Res."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1004","DOI":"10.1038\/nn1733","article-title":"Maternal presence serves as a switch between learning fear and attraction in infancy","volume":"9","author":"Moriceau","year":"2006","journal-title":"Nat. Neurosci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"508","DOI":"10.2307\/1131829","article-title":"Behavioral inhibition and stress reactivity: the moderating role of attachment security","volume":"67","author":"Nachmias","year":"1996","journal-title":"Child Dev."},{"key":"B29","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.expneurol.2017.04.017","article-title":"The valproic acid-induced rodent model of autism","volume":"299","author":"Nicolini","year":"2018","journal-title":"Exp. Neurol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1038\/sj.npp.1300518","article-title":"Behavioral alterations in rats prenatally to valproic acid: animal model of autism","volume":"30","author":"Schneider","year":"2005","journal-title":"Neuropsychopharmacology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.jaac.2017.01.012","article-title":"Age at first identification of autism spectrum disorder: an analysis of two US surveys","volume":"56","author":"Sheldrick","year":"2017","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"B32","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.yhbeh.2007.06.004","article-title":"Maternal attenuation of hypothalamic paraventricular nucleus norepinephrine switches avoidance learning to preference learning in preweanling rat pups","volume":"52","author":"Shionoya","year":"2007","journal-title":"Horm. Behav."},{"key":"B33","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/nmeth.2935","article-title":"Olfactory exposure to males, including men, causes stress and related analgesia in rodents","volume":"11","author":"Sorge","year":"2014","journal-title":"Nat. Methods"},{"key":"B34","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1002\/dev.420230504","article-title":"Inhibition of infant glucocorticoid stress response: specific role of maternal cues","volume":"23","author":"Stanton","year":"1990","journal-title":"Dev. Psychobiol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1002\/dev.420200204","article-title":"Maternal contact inhibits pituitary-adrenal stress responses in preweanling rats","volume":"20","author":"Stanton","year":"1987","journal-title":"Dev. Psychobiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/0165-3806(93)90022-3","article-title":"Maternal regulation of the hypothalamic-pituitary-adrenal axis in the infant rat: the roles of feeding and stroking","volume":"75","author":"Suchecki","year":"1993","journal-title":"Brain Res. Dev. Brain Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1196\/annals.1301.038","article-title":"Mother lowers glucocorticoid levels of preweaning rats after acute threat","volume":"1008","author":"Wiedenmayer","year":"2003","journal-title":"Ann. N Y Acad. Sci."},{"key":"B38","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.ijdevneu.2004.05.001","article-title":"Behavioral manifestations of autism in the first year of life","volume":"23","author":"Zwaigenbaum","year":"2005","journal-title":"Int. J. Dev. Neurosci."}],"container-title":["Frontiers in Behavioral Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2022.959485\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,8,22]],"date-time":"2022-08-22T05:32:59Z","timestamp":1661146379000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnbeh.2022.959485\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,22]]},"references-count":38,"alternative-id":["10.3389\/fnbeh.2022.959485"],"URL":"https:\/\/doi.org\/10.3389\/fnbeh.2022.959485","relation":{},"ISSN":["1662-5153"],"issn-type":[{"value":"1662-5153","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,22]]},"article-number":"959485"}}