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While our knowledge on the persistent effects of early\u2010life stress on hippocampal structure and function and the underlying mechanisms has advanced over the recent years, the molecular basis of the immediate postnatal stress effects on hippocampal development remains to be investigated. Here, we reported that repeated blockade of corticotropin\u2010releasing hormone receptor 1 (CRHR1) ameliorated postnatal stress\u2010induced hippocampal synaptic abnormalities in neonatal mice. Following the stress exposure, pups with fragmented maternal care showed retarded dendritic outgrowth and spine formation in CA3 pyramidal neurons and reduced hippocampal levels of synapse\u2010related proteins. During the stress exposure, repeated blockade of glucocorticoid receptors (GRs) by daily administration of RU486 (100 \u00b5g g<jats:sup>\u22121<\/jats:sup>) failed to attenuate postnatal stress\u2010evoked synaptic impairments. Conversely, daily administration of the CRHR1 antagonist antalarmin hydrochloride (20 \u00b5g g<jats:sup>\u22121<\/jats:sup>) in stressed pups normalized hippocampal protein levels of synaptophysin, postsynaptic density\u201095, nectin\u20101, and nectin\u20103, but not the <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:sc>d<\/jats:sc>\u2010aspartate receptor subunits NR1 and NR2A. Additionally, GR or CRHR1 antagonism attenuated postnatal stress\u2010induced endocrine alterations but not body growth retardation. Our data indicate that the CRH\u2010CRHR1 system modulates the deleterious effects of early\u2010life stress on dendritic development, spinogenesis, and synapse formation, and that early interventions of this system may prevent stress\u2010induced hippocampal maldevelopment. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/hipo.22254","type":"journal-article","created":{"date-parts":[[2014,2,4]],"date-time":"2014-02-04T02:10:02Z","timestamp":1391479802000},"page":"528-540","source":"Crossref","is-referenced-by-count":75,"title":["Blockade of corticotropin\u2010releasing hormone receptor 1 attenuates early\u2010life stress\u2010induced synaptic abnormalities in the neonatal hippocampus"],"prefix":"10.1002","volume":"24","author":[{"given":"Xue\u2010Mei","family":"Liao","sequence":"first","affiliation":[{"name":"Institute of Mental Health Peking University 100191 Beijing China"},{"name":"Key Laboratory for Mental Health, Ministry of Health (Peking University) 100191 Beijing 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of Health (Peking University) 100191 Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao\u2010Meng","family":"Xie","sequence":"additional","affiliation":[{"name":"Institute of Mental Health Peking University 100191 Beijing China"},{"name":"Key Laboratory for Mental Health, Ministry of Health (Peking University) 100191 Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010Ai","family":"Su","sequence":"additional","affiliation":[{"name":"Institute of Mental Health Peking University 100191 Beijing China"},{"name":"Key Laboratory for Mental Health, Ministry of Health (Peking University) 100191 Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias V.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Psychiatry, RG Neurobiology of Stress 80804 Munich 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