{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T06:09:49Z","timestamp":1760854189088,"version":"3.41.2"},"reference-count":95,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T00:00:00Z","timestamp":1616025600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Severe early life stress has long been associated with neuropsychological disorders in adulthood, including depression, schizophrenia, post-traumatic stress disorder, and memory dysfunction. To some extent, all of these conditions involve dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and reduced negative feedback inhibition of cortisol release in adulthood. However, the time course for mental health and hormonal outcomes across life stages and the attributes of early life stress that direct the behavioral and biological alterations is not fully understood. We designed our studies to compare outcomes of the two most common maternal deprivation schedules on cognitive ability prior to adulthood. We exposed rat pups to daily or randomly spaced maternal separation bouts within the first 3 weeks of life and examined cognitive performance, neurotrophic signaling, and stress and immune system markers during puberty. We found that the daily separation schedule impaired spatial learning while the randomly spaced schedule did not alter maze performance relative to normally reared control animals. Animals that underwent daily separation showed a tendency for reduced body weight compared to the randomly spaced condition, but there were no differences in adrenal weight. Thymus weight normalized by body weight was increased following daily separation compared to random separation and control conditions. Plasma corticosterone levels measured after behavior testing did not differ amongst experimental groups and there was no impact of TrKB receptor inhibition. Combined, the results show that different early life stress schedules produce different behavioral and biological outcomes when measured at puberty. Combined with prior findings from more mature animals, the results presented here suggest that daily neonatal stress produces varied alterations in spatial cognition at different life stages with a transient learning deficit at puberty preceding a more persistent and a progressive memory impairment through adulthood and into aging.<\/jats:p>","DOI":"10.3389\/fcell.2021.621308","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T04:52:00Z","timestamp":1616043120000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Spatial Learning Is Impaired in Male Pubertal Rats Following Neonatal Daily but Not Randomly Spaced Maternal Deprivation"],"prefix":"10.3389","volume":"9","author":[{"given":"Emily T.","family":"Stoneham","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel G.","family":"McHail","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabina","family":"Samipour-Biel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Liehr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina M.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean C.","family":"Evans","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katelyn","family":"Boggs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Theodore C.","family":"Dumas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,18]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1016\/j.psyneuen.2006.12.013","article-title":"Cognitive impairment associated to HPA axis hyperactivity after maternal separation in rats.","volume":"32","author":"Aisa","year":"2007","journal-title":"Psychoneuroendocrinology"},{"key":"B2","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S0736-5748(98)00025-2","article-title":"Do early-life events permanently alter behavioral and hormonal responses to stressors?","volume":"16","author":"Anisman","year":"1998","journal-title":"Int. J. Dev. Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.neubiorev.2004.06.009","article-title":"Social factors and individual vulnerability to chronic stress exposure.","volume":"29","author":"Bartolomucci","year":"2005","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B4","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1037\/0735-7044.111.2.267","article-title":"Spatial learning and memory at defined points of the estrous cycle: effects on performance of a hippocampal-dependent task.","volume":"111","author":"Berry","year":"1997","journal-title":"Behav. Neurosci."},{"key":"B5","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.cobeha.2016.12.012","article-title":"New insights into early-life stress and behavioral outcomes.","volume":"14","author":"Bolton","year":"2017","journal-title":"Curr. Opin. Behav. Sci."},{"key":"B6","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/S0962-1849(01)80014-7","article-title":"Loss and human resilience.","volume":"10","author":"Bonanno","year":"2002","journal-title":"Appl. Preven. Psychol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.bbr.2018.02.020","article-title":"Daily maternal separations during stress hyporesponsive period decrease the thresholds of panic-like behaviors to electrical stimulation of the dorsal periaqueductal gray of the adult rat.","volume":"344","author":"Borges-Aguiar","year":"2018","journal-title":"Behav. Brain Res."},{"key":"B8","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.yhbeh.2011.03.011","article-title":"Behavioral effects of chronic adolescent stress are sustained and sexually dimorphic.","volume":"60","author":"Bourke","year":"2011","journal-title":"Horm. Behav."},{"key":"B9","doi-asserted-by":"publisher","first-page":"9328","DOI":"10.1523\/JNEUROSCI.2281-05.2005","article-title":"Mechanisms of late-onset cognitive decline after early-life stress.","volume":"25","author":"Brunson","year":"2005","journal-title":"J. Neurosci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"9328","DOI":"10.1523\/JNEUROSCI.2281-05.2005","article-title":"Mechanisms of late-onset cognitive decline after early-life stress.","volume":"25","author":"Brunson","year":"2005","journal-title":"J. Neurosci."},{"key":"B11","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1542\/peds.26.5.762","article-title":"Regrowth and overgrowth of the thymus after atrophy induced by the oral administration of adrenocorticosteroids to human infants.","volume":"26","author":"Caffey","year":"1960","journal-title":"Pediatrics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1016\/j.cobeha.2017.01.001","article-title":"The effects of stress in early life and adolescence on posttraumatic stress disorder, depression, and anxiety symptomatology in adulthood.","volume":"14","author":"Chaby","year":"2017","journal-title":"Curr. Opin. Behav. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.yfrne.2008.03.003.Epigenetic","article-title":"Epigenetic mechanisms and the transgenerational effects of maternal care.","volume":"29","author":"Champagne","year":"2008","journal-title":"Front. Neuroendocr."},{"key":"B14","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1002\/dev.10066","article-title":"Effects of pre- and postnatal stimulation on developmental, emotional, and cognitive aspects in rodents: a review.","volume":"41","author":"Chapillon","year":"2002","journal-title":"Dev. Psychobiol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"599","DOI":"10.1016\/j.neubiorev.2010.07.003","article-title":"Altering BDNF expression by genetics and\/or environment: Impact for emotional and depression-like behaviour in laboratory mice.","volume":"35","author":"Chourbaji","year":"2010","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B16","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1016\/S0166-4328(02)00270-X","article-title":"Massed but not spaced training impairs spatial memory.","volume":"139","author":"Commins","year":"2003","journal-title":"Behav. Brain Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.yhbeh.2011.04.003","article-title":"The newborn rat\u2019s stress system readily habituates to repeated and prolonged maternal separation, while continuing to respond to stressors in context dependent fashion.","volume":"60","author":"Daskalakis","year":"2011","journal-title":"Horm. Behav."},{"key":"B18","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.neubiorev.2004.10.008","article-title":"Stress, genes and the mechanism of programming the brain for later life.","volume":"29","author":"De Kloet","year":"2005","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1712","DOI":"10.1523\/JNEUROSCI.4402-09.2010","article-title":"Anti-glucocorticoid gene therapy reverses the impairing effects of elevated corticosterone on spatial memory, hippocampal neuronal excitability, and synaptic plasticity.","volume":"30","author":"Dumas","year":"2010","journal-title":"J. Neurosci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.chiabu.2011.10.006","article-title":"The economic burden of child maltreatment in the united states and implications for prevention.","volume":"36","author":"Fang","year":"2012","journal-title":"Child Abus. Negl."},{"key":"B21","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/S0306-4530(00)00060-3","article-title":"Individual differences in the recovery of the hypothalamic-pituitary-adrenal axis after termination of exposure to a severe stressor in outbred male sprague-dawley rats.","volume":"26","author":"Garc\u00eda","year":"2001","journal-title":"Psychoneuroendocrinology"},{"key":"B22","doi-asserted-by":"publisher","first-page":"E1105","DOI":"10.1152\/ajpendo.00529.2012","article-title":"Effects of prolonged exendin-4 administration on hypothalamic-pituitary-adrenal axis activity and water balance.","volume":"304","author":"Gil-Lozano","year":"2013","journal-title":"AJP Endocrinol. Metab."},{"key":"B23","doi-asserted-by":"publisher","first-page":"3055","DOI":"10.1093\/jn\/131.10.3055","article-title":"Stress during labor and delivery is associated with delayed onset of lactation among urban guatemalan women.","volume":"132","author":"Grajeda","year":"2002","journal-title":"J. Nutr."},{"key":"B24","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1002\/jnr.20418","article-title":"Increased adult hippocampal brain-derived neurotrophic factor and normal levels of neurogenesis in maternal separation rats.","volume":"79","author":"Greisen","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"641","DOI":"10.1038\/sj.npp.1300397","article-title":"Importance of studying the contributions of early adverse experience to neurobiological findings in depression.","volume":"29","author":"Heim","year":"2004","journal-title":"Neuropsychopharmacology"},{"key":"B26","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1002\/cphy.c150015.Regulation","article-title":"Regulation of the hypothalamic-pituitary-adrenocortical stress response.","volume":"6","author":"Herman","year":"2016","journal-title":"Compr. Physiol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.biopsych.2019.04.028","article-title":"Sex Differences in vulnerability and resilience to stress across the life span.","volume":"86","author":"Hodes","year":"2019","journal-title":"Biol. Psychiatry"},{"key":"B28","doi-asserted-by":"crossref","first-page":"557","DOI":"10.33549\/physiolres.933530","article-title":"The effect of neonatal maternal stress on plasma levels of adrenocorticotropic hormone, corticosterone, leptin, and ghrelin in adult male rats exposed to acute heterotypic stressor.","volume":"65","author":"Holubov\u00e1","year":"2016","journal-title":"Physiol. Res."},{"key":"B29","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/S0006-8993(02)02985-2","article-title":"Neonatal maternal separation reduces hippocampal mossy fiber density in adult long evans rats.","volume":"950","author":"Huot","year":"2002","journal-title":"Brain Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1038\/aps.2015.94","article-title":"Formation of aversive memories associated with conditioned drug withdrawal requires BDNF expression in the amygdala in acute morphine-dependent rats.","volume":"36","author":"Ju","year":"2015","journal-title":"Acta Pharmacol. Sin."},{"key":"B31","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.neubiorev.2016.05.016","article-title":"The water maze paradigm in experimental studies of chronic cognitive disorders: theory, protocols, analysis, and inference.","volume":"68","author":"Kapadia","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B32","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.tins.2005.01.009","article-title":"Stress in early life inhibits neurogenesis in adulthood.","volume":"28","author":"Karten","year":"2005","journal-title":"Trends Neurosci."},{"key":"B33","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S1056-8719(97)00105-6","article-title":"Intracerebroventricular injection-induced increase in plasma corticosterone levels in the mouse: a stress model.","volume":"39","author":"Kim","year":"1998","journal-title":"J. Pharmacol. Toxicol. Methods"},{"key":"B34","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1038\/nrn849","article-title":"The stressed hippocampus, synaptic plasticity and lost memories.","volume":"3","author":"Kim","year":"2002","journal-title":"Nat. Rev. Neurosci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1016\/S0278-5846(01)00297-4","article-title":"The effects of stress exposure on the hypothalamic\u2013pituitary\u2013adrenal axis, thymus, thyroid hormones and glucose levels.","volume":"26","author":"Kioukia-Fougia","year":"2002","journal-title":"Prog. Neuro Psychopharmacol. Biol. Psychiatry"},{"key":"B36","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1016\/j.yhbeh.2004.01.005","article-title":"Shifts in preferred learning strategy across the estrous cycle in female rats.","volume":"45","author":"Korol","year":"2004","journal-title":"Horm. Behav."},{"key":"B37","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.brainres.2006.03.009","article-title":"Early life stress impairs fear conditioning in adult male and female rats.","volume":"1087","author":"Kosten","year":"2006","journal-title":"Brain Res."},{"key":"B38","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/S0736-5748(98)00034-3","article-title":"Responses to maternal separation: mechanisms and mediators.","volume":"16","author":"Kuhn","year":"1998","journal-title":"Int. J. Dev. Neurosci."},{"key":"B39","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1016\/j.biopsych.2003.10.007","article-title":"Long-term adaptations in glucocorticoid receptor and mineralocorticoid receptor mRNA and negative feedback on the hypothalamo-pituitary-adrenal axis following neonatal maternal separation.","volume":"55","author":"Ladd","year":"2004","journal-title":"Biol. Psychiatry"},{"key":"B40","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/j.psyneuen.2004.12.004","article-title":"Differential neuroendocrine responses to chronic variable stress in adult long evans rats exposed to handling-maternal separation as neonates.","volume":"30","author":"Ladd","year":"2005","journal-title":"Psychoneuroendocrinology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/j.lfs.2012.01.021","article-title":"Neonatal repetitive maternal separation causes long-lasting alterations in various neurotrophic factor expression in the cerebral cortex of rats.","volume":"90","author":"Lee","year":"2012","journal-title":"Life Sci."},{"key":"B42","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1515\/REVNEURO.2000.11.4.383","article-title":"Long-term biobehavioral effects of maternal separation in the rat: consistent or confusing?","volume":"11","author":"Lehmann","year":"2000","journal-title":"Rev. Neurosci."},{"key":"B43","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/S0091-3057(99)00150-1","article-title":"The maternal separation paradigm and adult emotionality and cognition in male and female wistar rats.","volume":"64","author":"Lehmann","year":"1999","journal-title":"Pharmacol. Biochem. Behav."},{"key":"B44","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/S0014-2999(00)00548-3","article-title":"Influence of psychological variables on the activity of the hypothalamic-pituitary-adrenal axis.","volume":"405","author":"Levine","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0031-9384(67)90011-X","article-title":"Physiological and behavioral effects of infantile stimulation.","volume":"2","author":"Levine","year":"1967","journal-title":"Physiol. Behav."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1016\/j.neurobiolaging.2005.09.031","article-title":"Salivary cortisol and memory function in human aging.","volume":"27","author":"Li","year":"2006","journal-title":"Neurobiol. Aging"},{"key":"B47","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.jchemneu.2010.07.001","article-title":"Single-prolonged stress induced mitochondrial-dependent apoptosis in hippocampus in the rat model of post-traumatic stress disorder.","volume":"40","author":"Li","year":"2010","journal-title":"J. Chem. Neuroanat."},{"key":"B48","doi-asserted-by":"publisher","first-page":"3091","DOI":"10.1111\/j.1460-9568.2007.05522.x","article-title":"Long-term behavioural and molecular alterations associated with maternal separation in rats.","volume":"25","author":"Lippmann","year":"2007","journal-title":"Eur. J. Neurosci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.yhbeh.2010.03.010","article-title":"Maternal separation modulates short-term behavioral and physiological indices of the stress response.","volume":"58","author":"Litvin","year":"2010","journal-title":"Horm. Behav."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/neuro.07.004.2009","article-title":"What is the most sensitive measure of water maze probe test performance?","volume":"3","author":"Maei","year":"2009","journal-title":"Front. Integr. Neurosci."},{"key":"B51","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/0306-4522(95)00256-I","article-title":"Stress-induced atrophy of apical dendrites of hippocampal CA3c neurons: comparison of stressors.","volume":"69","author":"Margarinos","year":"1995","journal-title":"Neuroscience"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1038\/nn.4086","article-title":"Mechanisms of stress in the brain.","volume":"18","author":"McEwen","year":"2015","journal-title":"Nat. Neurosci."},{"key":"B53","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S0924-977X(97)00064-3","article-title":"Prevention of stress-induced morphological and cognitive consequences.","volume":"7","author":"McEwen","year":"1997","journal-title":"Eur. Neuropsychopharmacol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/0197-4580(91)90036-J","article-title":"Postnatal handling attenuates certain neuroendocrine, anatomical, and cognitive dysfunctions associated with aging in female rats.","volume":"12","author":"Meaney","year":"1991","journal-title":"Neurobiol. Aging"},{"key":"B55","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1037\/a0034187","article-title":"Early postnatal handling alters glucocorticoid receptor concentrations in selected brain regions.","volume":"99","author":"Meaney","year":"1985","journal-title":"Behav. Neurosci."},{"key":"B56","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1046\/j.1365-2826.1999.00409.x","article-title":"The influence of postnatal handling on adult neuroendocrine and behavioural stress reactivity.","volume":"11","author":"Meerlo","year":"1999","journal-title":"J. Neuroendocrinol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.ygcen.2012.09.024","article-title":"Effects of early life stress on brain activity: implications from maternal separation model in rodents.","volume":"181","author":"Nishi","year":"2013","journal-title":"Gen. Comp. Endocrinol."},{"key":"B58","first-page":"2061","article-title":"Puberty in the Rat","author":"Ojeda","year":"2006","journal-title":"Physiology of Reproduction"},{"key":"B59","doi-asserted-by":"publisher","first-page":"6635","DOI":"10.1523\/JNEUROSCI.0247-10.2010","article-title":"Severe early life stress hampers spatial learning and neurogenesis, but improves hippocampal synaptic plasticity and emotional learning under high-stress conditions in adulthood.","volume":"30","author":"Oomen","year":"2010","journal-title":"J. Neurosci."},{"key":"B60","doi-asserted-by":"publisher","first-page":"S37","DOI":"10.1016\/j.brainres.2009.08.069","article-title":"Two repeated maternal separation procedures differentially affect brain 5-hydroxytryptamine transporter and receptors in young and adult male and female rats.","volume":"1305","author":"Oreland","year":"2009","journal-title":"Brain Res."},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.3389\/fnbeh.2019.00197","article-title":"How early life stress impact maternal care: a systematic review of rodent studies.","volume":"13","author":"Orso","year":"2019","journal-title":"Front. Behav. Neurosci."},{"key":"B62","doi-asserted-by":"publisher","first-page":"199","DOI":"10.3920\/BM2011.0015","article-title":"BDNF expression in the hippocampus of maternally separated rats: does Bifidobacterium breve 6330 alter BDNF levels?","volume":"2","author":"O\u2019Sullivan","year":"2011","journal-title":"Benef. Microbes"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1016\/j.neubiorev.2008.03.005","article-title":"What do we know about the long-term consequences of stress on ageing and the progression of age-related neurodegenerative disorders?","volume":"32","author":"Pardon","year":"2008","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B64","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1111\/pcn.12609","article-title":"Effects of maternal separation and antidepressant drug on epigenetic regulation of the brain-derived neurotrophic factor exon I promoter in the adult rat hippocampus.","volume":"72","author":"Park","year":"2018","journal-title":"Psychiatry Clin. Neurosci."},{"key":"B65","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1016\/j.physbeh.2008.09.004","article-title":"Reproductive experience alters corticosterone and CBG levels in the rat dam.","volume":"96","author":"Pawluski","year":"2009","journal-title":"Physiol. Behav."},{"key":"B66","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1037\/bne0000078.Using","article-title":"Using the spatial learning index to evaluate performance on the water maze.","volume":"129","author":"Pereira","year":"2015","journal-title":"Behav. Neurosci."},{"key":"B67","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0169-328X(93)90189-V","article-title":"Early, postnatal experience alters hypothalamic corticotropin-releasing factor (CRF) mRNA, median eminence CRF content and stress-induced release in adult rats.","volume":"18","author":"Plotsky","year":"1993","journal-title":"Brain Res. Mol. Brain Res."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00213-011-2217-4","article-title":"Editorial: early life stress and psychopharmacology.","volume":"214","author":"Price","year":"2011","journal-title":"Psychopharmacology (Berl)."},{"key":"B69","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1002\/dev.1018","article-title":"Comparison of the effects of early handling and early deprivation on maternal care in the rat.","volume":"38","author":"Pryce","year":"2001","journal-title":"Dev. Psychobiol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1037\/0735-7044.117.5.883","article-title":"Comparison of the effects of early handling and early deprivation on conditioned stimulus, context, and spatial learning and memory in adult rats.","volume":"117","author":"Pryce","year":"2003","journal-title":"Behav. Neurosci."},{"key":"B71","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1210\/en.2006-0983","article-title":"Adrenal insufficiency and colonic inflammation after a novel chronic psycho-social stress paradigm in mice: Implications and mechanisms.","volume":"148","author":"Reber","year":"2007","journal-title":"Endocrinology"},{"key":"B72","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1097\/FBP.0000000000000324","article-title":"Maternal separation induces long-term effects on monoamines and brain-derived neurotrophic factor levels on the frontal cortex, amygdala, and hippocampus: differential effects after a stress challenge.","volume":"28","author":"R\u00e9camier-Carballo","year":"2017","journal-title":"Behav. Pharmacol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1159\/000084203","article-title":"Differential stress reactivity in intact and ovariectomized prepubertal and adult female rats.","volume":"80","author":"Romeo","year":"2004","journal-title":"Neuroendocrinology"},{"key":"B74","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1016\/S0079-6123(08)63163-5","article-title":"Glucocorticoids and hippocampal damage.","volume":"10","author":"Sapolsky","year":"1987","journal-title":"Trends Neurosci."},{"key":"B75","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1007\/s00213-010-2096-0","article-title":"Early life stress paradigms in rodents: potential animal models of depression?","volume":"214","author":"Schmidt","year":"2011","journal-title":"Psychopharmacology (Berl)."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms21176331","article-title":"Effects of early life stress on epigenetic changes of the glucocorticoid receptor 17 promoter during adulthood.","volume":"21","author":"Seo","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B77","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.neuropharm.2016.02.009","article-title":"Early life stress increases stress vulnerability through BDNF gene epigenetic changes in the rat hippocampus.","volume":"105","author":"Seo","year":"2016","journal-title":"Neuropharmacology"},{"key":"B78","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/0166-4328(90)90165-B","article-title":"The effect of neonatal exposure to chronic footshock on pain-responsiveness and sensitivity to morphine after maturation in the rat.","volume":"36","author":"Shimada","year":"1990","journal-title":"Behav. Brain Res."},{"key":"B79","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1620\/tjem.235.81.Correspondence","article-title":"Blunted behavioral and molecular responses to chronic mild stress in adult rats with experience of infancy maternal separation.","volume":"235","author":"Shu","year":"2015","journal-title":"Tohoku J. Exp. Med."},{"key":"B80","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1037\/0735-7044.102.5.692","article-title":"Maternal deprivation potentiates pituitary-adrenal stress responses in infant rats.","volume":"102","author":"Stanton","year":"1988","journal-title":"Behav. Neurosci."},{"key":"B81","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.biopsych.2012.10.023","article-title":"Early stress evokes age-dependent biphasic changes in hippocampal neurogenesis, BDNF expression, and cognition.","volume":"73","author":"Suri","year":"2013","journal-title":"Biol. Psychiatry"},{"key":"B82","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.neubiorev.2016.06.021","article-title":"An overview of maternal separation effects on behavioural outcomes in mice: evidence from a four-stage methodological systematic review.","volume":"68","author":"Tractenberg","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B83","doi-asserted-by":"publisher","first-page":"E965","DOI":"10.1152\/ajpendo.00070.2006","article-title":"Chronic stress induces adrenal hyperplasia and hypertrophy in a subregion-specific manner.","volume":"291","author":"Ulrich-Lai","year":"2006","journal-title":"Am. J. Physiol. Metab."},{"key":"B84","doi-asserted-by":"publisher","first-page":"2838","DOI":"10.1210\/en.139.6.2838","article-title":"The ontogeny of glucocorticoid negative feedback: influence of maternal deprivation.","volume":"139","author":"van Oers","year":"1998","journal-title":"Endocrinology"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-020-0856-0","article-title":"Systematic review and meta-analysis: effects of maternal separation on anxiety-like behavior in rodents.","volume":"10","author":"Wang","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"B86","doi-asserted-by":"publisher","first-page":"13763","DOI":"10.1523\/JNEUROSCI.1991-12.2012","article-title":"Extinction of aversive memories associated with morphine withdrawal requires ERK-mediated epigenetic regulation of brain-derived neurotrophic factor transcription in the rat ventromedial prefrontal cortex.","volume":"32","author":"Wang","year":"2012","journal-title":"J. Neurosci."},{"key":"B87","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1037\/\/0735-7044.111.2.259","article-title":"Spatial and nonspatial learning across the rat estrous cycle.","volume":"111","author":"Warren","year":"1997","journal-title":"Behav. Neurosci."},{"key":"B88","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/nn1276","article-title":"Epigenetic programming by maternal behavior.","volume":"7","author":"Weaver","year":"2004","journal-title":"Nat. Neurosci."},{"key":"B89","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1016\/j.jpain.2007.07.001","article-title":"Maternal separation leads to persistent reductions in pain sensitivity in female rats.","volume":"8","author":"Weaver","year":"2007","journal-title":"J. Pain"},{"key":"B90","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1523\/JNEUROSCI.4986-10.2011","article-title":"The suppressive effect of an intra-prefrontal cortical infusion of BDNF on cocaine-seeking is TRK receptor and extracellular signal-regulated protein kinase mitogen-activated protein kinase dependent","volume":"31","author":"Whitfield","year":"2011","journal-title":"J. Neurosci."},{"key":"B91","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1002\/cne.903360210","article-title":"Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat.","volume":"336","author":"Woolley","year":"1993","journal-title":"J. Comp. Neurol."},{"key":"B92","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1046\/j.1365-2826.2001.00668.x","article-title":"Differential and age-dependent effects of maternal deprivation on the hypothalamic-pituitary-adrenal axis of brown norway rats from youth to senescence.","volume":"13","author":"Workel","year":"2001","journal-title":"J. Neuroendocrinol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.brainres.2015.04.010","article-title":"Tuning hippocampal synapses by stress-hormones: relevance for emotional memory formation.","volume":"1621","author":"Xiong","year":"2015","journal-title":"Brain Res."},{"key":"B94","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3109\/10253890.2014.936005","article-title":"Effect of maternal separation and chronic stress on hippocampal-dependent memory in young adult rats: evidence for the match-mismatch hypothesis.","volume":"3890","author":"Zalosnik","year":"2014","journal-title":"Stress"},{"key":"B95","doi-asserted-by":"publisher","first-page":"R1648","DOI":"10.1152\/ajpregu.00301.2011","article-title":"Time-dependent mediators of HPA axis activation following live Escherichia coli.","volume":"301","author":"Zimomra","year":"2011","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."}],"container-title":["Frontiers in Cell and Developmental Biology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.621308\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,21]],"date-time":"2022-12-21T20:50:00Z","timestamp":1671655800000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcell.2021.621308\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,18]]},"references-count":95,"alternative-id":["10.3389\/fcell.2021.621308"],"URL":"https:\/\/doi.org\/10.3389\/fcell.2021.621308","relation":{},"ISSN":["2296-634X"],"issn-type":[{"type":"electronic","value":"2296-634X"}],"subject":[],"published":{"date-parts":[[2021,3,18]]},"article-number":"621308"}}