{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:58:41Z","timestamp":1792648721333,"version":"4.5.0"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The present study investigated the effects of social defeat stress on the behaviours and expressions of 78-kDa glucose-regulated protein (Grp78), CCAAT\/enhancer-binding protein (C\/EBP) homologous protein (CHOP) and choline acetyltransferase (Chat) in the brains of adolescent mice. Adolescent male C57BL\/6J mice were divided into two groups (susceptible and unsusceptible) after 10 d social defeat stress. In expt 1, behavioural tests were conducted and brains were processed for Western blotting on day 21 after stress. In expt 2, social avoidance tests were conducted and brains were subsequently processed for Western blotting on day 12 after stress. Chronic social defeat stress produced more pronounced depression-like behaviours such as decreased locomotion and social interaction, increased anxiety-like behaviours and immobility, and impaired memory performance in susceptible mice. Moreover, susceptible mice showed greater expression of Grp78 and CHOP in the amygdala (Amyg) on days 12 and 21 compared with the other groups. Susceptible and unsusceptible groups showed significant increases in Grp78 and CHOP expression in the prefrontal cortex (PFC) and hippocampus (Hipp) on day 12 compared with the control group; this persisted until day 21. The levels of Chat measured on days 12 and 21 were significantly lower in the PFC, Amyg and Hipp of all defeated mice compared with controls. The findings of the behavioural tests indicate that chronic social defeat in adolescents produces anxiety-like behaviours, social withdrawal, despair-like behaviours and cognitive impairment. The Grp78, CHOP and Chat results suggest that the selective response of endoplasmic reticulum stress proteins in the Amyg plays an important role in the vulnerability\u2013stress model of depression.<\/jats:p>","DOI":"10.1017\/s1461145713000060","type":"journal-article","created":{"date-parts":[[2013,2,27]],"date-time":"2013-02-27T08:21:29Z","timestamp":1361953289000},"page":"1635-1647","source":"Crossref","is-referenced-by-count":71,"title":["Effects of chronic social defeat stress on behaviour, endoplasmic reticulum proteins and choline acetyltransferase in adolescent mice"],"prefix":"10.1093","volume":"16","author":[{"given":"Guang-Biao","family":"Huang","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Chonbuk National University Medical School, Jeonju, Korea"},{"name":"Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Chonbuk National University Medical School, Jeonju, Korea"},{"name":"Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushma Shrestha","family":"Muna","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Chonbuk National University Medical School, Jeonju, Korea"},{"name":"Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarique Rajasaheb","family":"Bagalkot","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Chonbuk National University Medical School, Jeonju, Korea"},{"name":"Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Mei","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Chonbuk National University Medical School, Jeonju, Korea"},{"name":"Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Jung","family":"Chae","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Chonbuk National University Medical School and Institute for Medical Sciences, South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Chul","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Chonbuk National University Medical School, Jeonju, Korea"},{"name":"Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,8,1]]},"reference":[{"key":"2019101113492368300_ref1","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1037\/h0077848","article-title":"Syndrome produced by lesions of the amygdalain monkeys (Macaca mulatta)","volume":"95","author":"Aggleton","year":"1981","journal-title":"J Comp Physiol Psychol"},{"key":"2019101113492368300_ref2","volume-title":"Diagnostic and statistical manual of mental disorders","author":"APA","year":"1994","edition":"4th edn"},{"key":"2019101113492368300_ref3","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1126\/science.1120972","article-title":"Essential role of BDNF in the mesolimbic dopamine pathway in social defeat stress","volume":"311","author":"Berton","year":"2006","journal-title":"Science"},{"key":"2019101113492368300_ref4","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1016\/S0893-133X(99)00091-3","article-title":"Increased temporal cortex ER stress proteins in depressed subjects who died by suicide","volume":"22","author":"Bown","year":"2000","journal-title":"Neuropsychopharmacology"},{"key":"2019101113492368300_ref5","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.dr.2007.08.003","article-title":"The adolescent brain","volume":"28","author":"Casey","year":"2008","journal-title":"Dev Rev"},{"key":"2019101113492368300_ref6","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1196\/annals.1440.010","article-title":"The adolescent brain","volume":"1124","author":"Casey","year":"2008","journal-title":"Ann N Y Acad Sci"},{"key":"2019101113492368300_ref7","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.bbr.2010.02.023","article-title":"The cholinergic system and depression","volume":"221","author":"Dagyt\u00e9","year":"2011","journal-title":"Behav Brain Res"},{"key":"2019101113492368300_ref8","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/S0165-0173(01)00067-4","article-title":"Applications of the Morris water maze in the study of learning and memory","volume":"36","author":"D'Hooge","year":"2001","journal-title":"Brain Res Brain Res Rev"},{"key":"2019101113492368300_ref9","volume-title":"The Allen reference atlas, (book+CD-ROM): a digital color brain atlas of the C57BL\/6J male mouse","author":"Dong","year":"2008"},{"key":"2019101113492368300_ref10","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1016\/j.physbeh.2009.03.025","article-title":"Social and non-social anxiety in adolescent and adult rats after repeated restraint","volume":"97","author":"Doremus-Fitzwater","year":"2009","journal-title":"Physiol Behav"},{"key":"2019101113492368300_ref11","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1002\/dev.420100205","article-title":"A critical period for social isolation in the rat","volume":"10","author":"Einon","year":"1977","journal-title":"Dev Psychobiol"},{"key":"2019101113492368300_ref12","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.pnpbp.2003.09.028","article-title":"Impaired memory following predatory stress in mice is improved by fluoxetine","volume":"28","author":"El Hage","year":"2004","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"2019101113492368300_ref13","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1037\/0735-7044.115.3.515","article-title":"The effects of bilateral lesions of the amygdale on dyadic social interactions in rhesus monkeys (Macaca mulatta)","volume":"115","author":"Emery","year":"2001","journal-title":"Behav Neurosci"},{"key":"2019101113492368300_ref14","doi-asserted-by":"publisher","first-page":"326","DOI":"10.1002\/(SICI)1098-2795(199912)54:4<326::AID-MRD2>3.0.CO;2-3","article-title":"Upregulation of CHOP-10 (gadd153) expression in the mouse blastocyst as a response to stress","volume":"54","author":"Fontanier-Razzaq","year":"1999","journal-title":"Mol Reprod Dev"},{"key":"2019101113492368300_ref15","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1016\/0006-8993(78)90267-6","article-title":"Effects of repeated immobilization stress on glutamate decarboxylase and choline acetyltransferase in discrete brain regions","volume":"152","author":"Gottesfeld","year":"1978","journal-title":"Brain Res"},{"key":"2019101113492368300_ref16","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1016\/S0031-9384(98)00333-3","article-title":"Influence of age on behavioral response in the light\/dark paradigm","volume":"66","author":"Hasco\u00ebt","year":"1999","journal-title":"Physiol Behav"},{"key":"2019101113492368300_ref17","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1016\/0024-3205(77)90437-4","article-title":"Regulation of acetylcholine synthesis in nervous tissue","volume":"20","author":"Haubrich","year":"1977","journal-title":"Life Sci"},{"key":"2019101113492368300_ref18","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1017\/S1461145708009358","article-title":"Aberrant endoplasmic reticulum stress response in lymphoblastoid cells from patient with bipolar disorder","volume":"12","author":"Hayashi","year":"2009","journal-title":"Int J Neuropsychopharmacol"},{"key":"2019101113492368300_ref19","doi-asserted-by":"publisher","first-page":"10","DOI":"10.4236\/pp.2011.21002","article-title":"Restraint-induced expression of endoplasmic reticulum stress-related genes in the mouse brain","volume":"2","author":"Ishisaka","year":"2011","journal-title":"Pharmacol Pharm"},{"key":"2019101113492368300_ref20","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1126\/science.982031","article-title":"Regulation of acetylcholine synthesis, does cytoplasmic acetylcholine control high affinity choline uptake?","volume":"194","author":"Jenden","year":"1976","journal-title":"Science"},{"key":"2019101113492368300_ref21","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1136\/bmj.319.7206.348","article-title":"Bullying, depression, and suicidal ideation in Finnish adolescents, school survey","volume":"319","author":"Kaltiala-Heino","year":"1999","journal-title":"BMJ"},{"key":"2019101113492368300_ref22","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1192\/bjp.bp.108.049536","article-title":"Associations between childhood trauma, bullying and psychotic symptoms among a school-based adolescent sample","volume":"193","author":"Kelleher","year":"2008","journal-title":"Br J Psychiatry"},{"key":"2019101113492368300_ref23","doi-asserted-by":"publisher","first-page":"593","DOI":"10.1001\/archpsyc.62.6.593","article-title":"Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication","volume":"62","author":"Kessler","year":"2005","journal-title":"Arch Gen Psychiatry"},{"key":"2019101113492368300_ref24","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1515\/IJAMH.2008.20.2.133","article-title":"Bullying and suicide, a review","volume":"20","author":"Kim","year":"2008","journal-title":"Int J Adolesc Med Health"},{"key":"2019101113492368300_ref25","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.bbi.2006.11.001","article-title":"Repeated social defeat causes increased anxiety-like behavior and alters splenocyte function in C57BL\/6 and CD-1 mice","volume":"21","author":"Kinsey","year":"2007","journal-title":"Brain Behav Immun"},{"key":"2019101113492368300_ref26","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.cell.2007.09.018","article-title":"Molecular adaptations underlying susceptibility and resistance to social defeat in brain reward regions","volume":"131","author":"Krishnan","year":"2007","journal-title":"Cell"},{"key":"2019101113492368300_ref27","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.bbr.2007.09.005","article-title":"Effects of chronic social stress in adolescence on anxiety and neuroendocrine response to mild stress in male and female rats","volume":"187","author":"McCormick","year":"2008","journal-title":"Behav Brain Res"},{"key":"2019101113492368300_ref28","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1016\/j.neubiorev.2005.03.014","article-title":"Dominant-submissive behavior as model of mania and depression","volume":"29","author":"Malatynska","year":"2005","journal-title":"Neurosci Biobehav Rev"},{"key":"2019101113492368300_ref29","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1006\/excr.2001.5248","article-title":"Stress-inducible transcription factor CHOP\/gadd153 induces apoptosis in mammalian cells via p38 kinase-dependent and -independent mechanisms","volume":"267","author":"Maytin","year":"2001","journal-title":"Exp Cell Res"},{"key":"2019101113492368300_ref30","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/S0987-7053(03)00009-1","article-title":"The defense system of fear: behavior and neurocircuitry","volume":"33","author":"Misslin","year":"2003","journal-title":"Neurophysiol Clin"},{"key":"2019101113492368300_ref31","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.pbb.2012.05.002","article-title":"Differential severity of anxiogenic effects resulting from a brief swim or underwater trauma in adolescent male rats","volume":"102","author":"Moore","year":"2012","journal-title":"Pharmacol Biochem Behav"},{"key":"2019101113492368300_ref32","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1111\/j.1471-4159.2004.02952.x","article-title":"Sleep deprivation induces the unfolded protein response in mouse cerebral cortex","volume":"92","author":"Naidoo","year":"2005","journal-title":"J Neurochem"},{"key":"2019101113492368300_ref33","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1016\/j.biopsych.2005.09.018","article-title":"The mesolimbic dopamine reward circuit in depression","volume":"59","author":"Nestler","year":"2006","journal-title":"Biol Psychiatry"},{"key":"2019101113492368300_ref34","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1046\/j.1440-1827.1999.00977.x","article-title":"Choline acetyltransferase, the structure, distribution and pathologic changes in the central nervous system","volume":"49","author":"Oda","year":"1999","journal-title":"Pathol Int"},{"key":"2019101113492368300_ref35","doi-asserted-by":"publisher","first-page":"371","DOI":"10.4196\/kjpp.2010.14.6.371","article-title":"Effects of Glycyrrhizae Radix on repeated restraint stress-induced neurochemical and behavioral responses","volume":"14","author":"Park","year":"2010","journal-title":"Korean J Physiol Pharmacol"},{"key":"2019101113492368300_ref36","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1016\/j.bbr.2010.07.014","article-title":"Different susceptibility to social stress of BalbC and C57BL6\/J mice","volume":"216","author":"Razzoli","year":"2010","journal-title":"Behav Brain Res"},{"key":"2019101113492368300_ref37","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1037\/h0058870","article-title":"Influence of amygdalectomy on social behavior in monkeys","volume":"47","author":"Rosvold","year":"1954","journal-title":"J Comp Physiol Psychol"},{"key":"2019101113492368300_ref38","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1016\/j.bbr.2012.01.022","article-title":"Long-term behavioral consequences of stress exposure in adolescent vs. young adult rats","volume":"229","author":"Saul","year":"2012","journal-title":"Behav Brain Res"},{"key":"2019101113492368300_ref39","doi-asserted-by":"publisher","first-page":"1152","DOI":"10.1038\/mp.2010.34","article-title":"Environmental enrichment requires adult neurogenesis to facilitate the recovery from psychosocial stress","volume":"15","author":"Schloesser","year":"2010","journal-title":"Mol Psychiatry"},{"key":"2019101113492368300_ref40","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1016\/j.biopsych.2006.10.014","article-title":"Impaired endoplasmic reticulum stress response in B-lymphoblasts from patients with bipolar-I disorder","volume":"62","author":"So","year":"2007","journal-title":"Biol Psychiatry"},{"key":"2019101113492368300_ref41","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/S0149-7634(00)00014-2","article-title":"The adolescent brain and age-related behavioral manifestations","volume":"24","author":"Spear","year":"2000","journal-title":"Neurosci Biobehav Rev"},{"key":"2019101113492368300_ref42","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1002\/hipo.20655","article-title":"Chronic social stress during adolescence induces cognitive impairment in aged mice","volume":"20","author":"Sterlemann","year":"2010","journal-title":"Hippocampus"},{"key":"2019101113492368300_ref43","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/S0031-9384(97)00366-1","article-title":"Greater behavioral effects of stress in immature as compared to mature male mice","volume":"63","author":"Stone","year":"1997","journal-title":"Physiol Behav"},{"key":"2019101113492368300_ref44","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1038\/nn1659","article-title":"Sustained hippocampal chromatin regulation in a mouse model of depression and antidepressant action","volume":"9","author":"Tsankova","year":"2006","journal-title":"Nat Neurosci"},{"key":"2019101113492368300_ref45","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1016\/S0306-4530(98)00029-8","article-title":"Stress and the developing limbic-hypothalamic-pituitary adrenal axis","volume":"23","author":"V\u00e1zquez","year":"1998","journal-title":"Psychoneuroendocrinology"},{"key":"2019101113492368300_ref46","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/S0166-4328(00)00300-4","article-title":"Defeat followed by individual hosing results in long-term impaired reward- and cognition-related behaviors in rats","volume":"117","author":"Von Frijtag","year":"2000","journal-title":"Behav Brain Res"},{"key":"2019101113492368300_ref47","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1007\/BF01930471","article-title":"Effect of stress on choline acetyltransferase activity of the brain and the adrenal of the rat","volume":"48","author":"Wahba","year":"1992","journal-title":"Experientia"},{"key":"2019101113492368300_ref48","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1111\/j.1365-2826.1995.tb00799.x","article-title":"Dissociation between behavioral and hormonal responses to the forced swim stress in lactating rats","volume":"7","author":"Walker","year":"1995","journal-title":"J Neuroendocrinol"},{"key":"2019101113492368300_ref49","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1016\/0278-5846(90)90073-P","article-title":"Neurobehavioral studies of forced swimming, the role of learning and memory in the forced swim test","volume":"14","author":"West","year":"1990","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"2019101113492368300_ref50","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1046\/j.1471-4159.1994.62051653.x","article-title":"Choline acetyltransferase, celebrating its fiftieth year","volume":"62","author":"Wu","year":"1994","journal-title":"J Neurochem"},{"key":"2019101113492368300_ref51","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1017\/S1461145710000945","article-title":"Cognitive and neural correlates of depression-like behavior in socially defeated mice, an animal model of depression with cognitive dysfunction","volume":"14","author":"Yu","year":"2011","journal-title":"Int J Neuropsychopharmacol"}],"container-title":["International Journal of Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ijnp\/article-pdf\/16\/7\/1635\/30135330\/16-7-1635.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ijnp\/article-pdf\/16\/7\/1635\/30135330\/16-7-1635.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,6]],"date-time":"2024-05-06T14:37:36Z","timestamp":1715006256000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ijnp\/article\/16\/7\/1635\/713538"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,8,1]]},"references-count":51,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2013,8,1]]}},"URL":"https:\/\/doi.org\/10.1017\/s1461145713000060","relation":{},"ISSN":["1469-5111","1461-1457"],"issn-type":[{"value":"1469-5111","type":"electronic"},{"value":"1461-1457","type":"print"}],"subject":[],"published-other":{"date-parts":[[2013,8]]},"published":{"date-parts":[[2013,8,1]]}}}