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This is negated in mice lacking the GluN2D subunit of the NMDAR, suggesting the GluN2D subunit mediates the hyperlocomotor effects of these drugs. However, the role of GluN2D in mediating other schizophrenia\u2010relevant NMDAR antagonist\u2010induced behavioral disturbances, and in both sexes, is unclear. This study aimed to investigate the role of the GluN2D subunit in mediating schizophrenia\u2010relevant behaviors induced by a range of NMDA receptor antagonists. Using both male and female GluN2D knockout (KO) mice, we examined the effects of the NMDAR antagonist's PCP, the S\u2010ketamine enantiomer (S\u2010ket), and the ketamine metabolite R\u2010norketamine (R\u2010norket) on locomotor activity, anxiety\u2010related behavior, and recognition and short\u2010term spatial memory. GluN2D\u2010KO mice showed a blunted locomotor response to R\u2010norket, S\u2010ket, and PCP, a phenotype present in both sexes. GluN2D\u2010KO mice of both sexes showed an anxious phenotype and S\u2010ket, R\u2010norket, and PCP showed anxiolytic effects that were dependent on sex and genotype. S\u2010ket disrupted spatial recognition memory in females and novel object recognition memory in both sexes, independent of genotype. This datum identifies a role for the GluN2D subunit in sex\u2010specific effects of NMDAR antagonists and on the differential effects of the R\u2010 and S\u2010ket enantiomers.<\/jats:p>","DOI":"10.1002\/jnr.25257","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T23:35:07Z","timestamp":1697067307000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Understanding the role of the\n                    <scp>NMDA<\/scp>\n                    receptor subunit,\n                    <scp>GluN2D<\/scp>\n                    , in mediating\n                    <scp>NMDA<\/scp>\n                    receptor antagonist\u2010induced behavioral disruptions in male and female mice"],"prefix":"10.1002","volume":"102","author":[{"given":"Chitra","family":"Vinnakota","sequence":"first","affiliation":[{"name":"Department of Psychiatry Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Schroeder","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8342-0278","authenticated-orcid":false,"given":"Kazutaka","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Addictive Substance Project Tokyo Metropolitan Institute of Medical Science  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soichiro","family":"Ide","sequence":"additional","affiliation":[{"name":"Addictive Substance Project Tokyo Metropolitan Institute of Medical Science  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayoshi","family":"Mishina","sequence":"additional","affiliation":[{"name":"Brain Science Laboratory, The Research Organization of Science and Technology Ritsumeikan University  Kusatsu Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Hudson","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nigel Charles","family":"Jones","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suresh","family":"Sundram","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Monash University  Clayton Victoria Australia"},{"name":"Mental Health Program Monash Health  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6111-355X","authenticated-orcid":false,"given":"Rachel Anne","family":"Hill","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Monash University  Clayton Victoria Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.903470112"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.16-01-00019.1996"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1176\/ajp.135.9.1081"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064-018-2526-7"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0261-20.2020"},{"key":"e_1_2_12_7_1","first-page":"351","volume-title":"Advances in pharmacology","author":"Balu D. 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