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In the present study, mice on postnatal day 21\u201328 were randomly assigned to either a group or isolated cages for 8 weeks. The socially isolated (SI) mice exhibited a higher level of spontaneous locomotor activity, a longer duration of immobility in the forced swimming test (FST), significantly less prepulse inhibition (PPI) and an increase in aggressive (but not attack) behavior. However, acute stress markedly exacerbated the attack counts of the SI mice but did not affect the group housing (GH) mice. SI mice exhibited higher synaptosomal NR<jats:sub>2A<\/jats:sub> and NR<jats:sub>2B<\/jats:sub> levels in the hippocampus as compared to the GH mice. Whole\u2010cell patch clamp recordings of CA1 neurons in hippocampal slices showed that the SI mice exhibited a higher input\u2010output relationship of NMDAR\u2010EPSCs as compared to the GH mice. Application of the NR<jats:sub>2B<\/jats:sub>\u2010specific antagonist ifenprodil produced a greater attenuating effect on NMDAR\u2010EPSCs in slices from the SI mice. NMDAR EPSCs recorded from the SI mice had a slower deactivation kinetic. MK\u2010801, CPP and ifenprodil, the NMDA antagonists, reversed acute stress\u2010induced exaggeration of aggressive and depressive behaviors. Furthermore, acute stress\u2010induced exacerbation of attack behavior in the SI mice was abolished after the knockdown of NR<jats:sub>2B<\/jats:sub> expression. These results suggest that social isolation\u2010induced increased expression of NMDA receptors in the hippocampus involves stress exacerbation of aggressive behaviors. Amelioration of aggressive behaviors by NMDA antagonists may open a new avenue for the treatment of psychopathologies that involve outbursts of emotional aggression in neglected children. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/hipo.22384","type":"journal-article","created":{"date-parts":[[2014,10,28]],"date-time":"2014-10-28T06:01:31Z","timestamp":1414476091000},"page":"474-485","source":"Crossref","is-referenced-by-count":75,"title":["Social isolation\u2010induced increase in <scp>NMDA<\/scp> receptors in the hippocampus exacerbates emotional dysregulation in mice"],"prefix":"10.1002","volume":"25","author":[{"given":"Chih\u2010Hua","family":"Chang","sequence":"first","affiliation":[{"name":"Institute of Basic Medical Science, National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Hsin","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology College of Medicine, National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology College of Medicine, National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang\u2010Jung","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Science, National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po\u2010Wu","family":"Gean","sequence":"additional","affiliation":[{"name":"Institute of Basic Medical Science, National Cheng Kung University  Tainan Taiwan"},{"name":"Department of Pharmacology College of Medicine, National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,11,5]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2007.09.019"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10130"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2004.06.009"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098-2337(1999)25:5<381::AID-AB6>3.0.CO;2-B"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2006.00280.x"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2013.00161"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-009-1543-2"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.11.033"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03843.x"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/stke.2552004re16"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3093"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2270481"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.05.022"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2011.11.004"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.08.044"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-9-111"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1330.012"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2008.03.003"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142301.ns0817s24"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2011.04.003"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471142301.ns0116s42"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn3042"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2005.08.006"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0145-2134(02)00341-1"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2010.03.021"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1601-183X.2010.00676.x"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004583-199205000-00001"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2008.06.023"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09736"},{"key":"e_1_2_5_31_1","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1037\/0003-066X.53.2.242","article-title":"Development of juvenile aggression and violence. 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