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Allosteric modulation represents an important mechanism for receptor functional regulation. In this study, we examined antidepressant activity of the latest identified novel and selective allosteric modulator of sigma\u20101 receptor 3\u2010methyl\u2010phenyl\u20102, 3, 4, 5\u2010tetrahydro\u20101H\u2010benzo[d]azepin\u20107\u2010ol (\n                      <jats:styled-content style=\"fixed-case\">SOMCL<\/jats:styled-content>\n                      \u2010668).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p>\n                      A single administration of\n                      <jats:styled-content style=\"fixed-case\">SOMCL<\/jats:styled-content>\n                      \u2010668 decreased the immobility time in the forced swimming test (FST) and tailing suspended test in mice, which were abolished by pretreatment of sigma\u20101 receptor antagonist\n                      <jats:styled-content style=\"fixed-case\">BD<\/jats:styled-content>\n                      1047. In the chronic unpredicted mild stress (\n                      <jats:styled-content style=\"fixed-case\">CUMS<\/jats:styled-content>\n                      ) model, chronic application of\n                      <jats:styled-content style=\"fixed-case\">SOMCL<\/jats:styled-content>\n                      \u2010668 rapidly ameliorated anhedonia\u2010like behavior (within a week), accompanying with the enhanced expression of brain\u2010derived neurotrophic factor (\n                      <jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content>\n                      ) and phosphorylation of glycogen synthase kinase 3\n                      <jats:italic>\u03b2<\/jats:italic>\n                      (\n                      <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\n                      3\n                      <jats:italic>\u03b2<\/jats:italic>\n                      ) (Ser\u20109) in the hippocampus.\n                      <jats:styled-content style=\"fixed-case\">SOMCL<\/jats:styled-content>\n                      \u2010668 also rapidly promoted the phosphorylation of\n                      <jats:styled-content style=\"fixed-case\">GSK<\/jats:styled-content>\n                      3\n                      <jats:italic>\u03b2<\/jats:italic>\n                      (Ser\u20109) in an allosteric manner\n                      <jats:italic>in\u00a0vitro<\/jats:italic>\n                      . In the cultured primary neurons,\n                      <jats:styled-content style=\"fixed-case\">SOMCL<\/jats:styled-content>\n                      \u2010668 enhanced the sigma\u20101 receptor agonist\u2010induced neurite outgrowth and the secretion of\n                      <jats:styled-content style=\"fixed-case\">BDNF<\/jats:styled-content>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">SOMCL<\/jats:styled-content>\n                      \u2010668, a novel allosteric modulator of sigma\u20101 receptors, elicits a potent and rapid acting antidepressant effect. The present data provide the first evidence that allosteric modulation of sigma\u20101 receptors may represent a new approach for antidepressant drug discovery.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.12502","type":"journal-article","created":{"date-parts":[[2016,2,8]],"date-time":"2016-02-08T04:08:26Z","timestamp":1454904506000},"page":"368-377","source":"Crossref","is-referenced-by-count":56,"title":["Allosteric Modulation of Sigma\u20101 Receptors Elicits Rapid Antidepressant Activity"],"prefix":"10.1111","volume":"22","author":[{"given":"Yun","family":"Wang","sequence":"first","affiliation":[{"name":"Jiangsu Key laboratory for Translational Research for Neuropsychiatric Diseases The Collaborative Innovation Center for Brain Science College of Pharmaceutical Sciences Soochow University Jiangsu China"},{"name":"Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Department of Pharmacology Xuzhou Medical College Jiangsu 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