{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T07:44:28Z","timestamp":1780731868045,"version":"3.54.1"},"reference-count":67,"publisher":"Cambridge University Press (CUP)","issue":"05","license":[{"start":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T00:00:00Z","timestamp":1561334400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.cambridge.org"],"crossmark-restriction":true},"short-container-title":["Acta Neuropsychiatr."],"published-print":{"date-parts":[[2019,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec id=\"S0924270819000255_as1\"><jats:title>Objectives:<\/jats:title><jats:p>Treatment-resistance to antidepressants is a major problem in the pharmacotherapy of major depressive disorder (MDD). Unfortunately, only a few animal models are suitable for studying treatment-resistant depression, among them repeated treatment with Adrenocorticotropic hormone (ACTH) appears to be useful to mimic treatment-resistance to monoaminergic antidepressants. Therefore, the present work aimed to investigate the effectiveness of s-ketamine and rapastinel (formerly GLYX13), modulators of the glutamatergic <jats:italic>N<\/jats:italic>-methyl-D-aspartate receptor in ACTH-treated animals.<\/jats:p><\/jats:sec><jats:sec id=\"S0924270819000255_as2\"><jats:title>Methods:<\/jats:title><jats:p>Na\u00efve male Sprague Dawley rats were subjected to repeated subcutaneous injections with ACTH (100 \u00b5g\/0.1 ml\/rat\/day) for 14 days and drug treatment on the test day (open field and forced swim test) with imipramine, s-ketamine or rapastinel. In addition, assessment of plasma levels of corticosterone and ACTH was carried out.<\/jats:p><\/jats:sec><jats:sec id=\"S0924270819000255_as3\"><jats:title>Results:<\/jats:title><jats:p>We found that rats repeatedly treated with ACTH for 14 days responded to single injections with s-ketamine (15 mg\/kg) and rapastinel (10 mg\/kg), but failed to respond to imipramine (15 mg\/kg). In the plasma, the levels of corticosterone and ACTH were increased after 14 days of daily treatment with ACTH, independently of the treatment.<\/jats:p><\/jats:sec><jats:sec id=\"S0924270819000255_as4\"><jats:title>Conclusion:<\/jats:title><jats:p>The present data confirm development of a resistance to treatment following chronic ACTH administration. In addition, the study confirms the possible effectiveness of s-ketamine and rapastinel as treatment options in treatment-resistant depression. Moreover, it highlights the importance of the glutamatergic system in the neurobiology of depression. Further studies are necessary to evaluate how repeated treatment with ACTH leads to a depressed condition resistant to monoaminergic antidepressants.<\/jats:p><\/jats:sec>","DOI":"10.1017\/neu.2019.25","type":"journal-article","created":{"date-parts":[[2019,6,24]],"date-time":"2019-06-24T03:29:50Z","timestamp":1561346990000},"page":"258-265","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":24,"title":["Esketamine and rapastinel, but not imipramine, have antidepressant-like effect in a treatment-resistant animal model of depression"],"prefix":"10.1017","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9051-3154","authenticated-orcid":false,"given":"Vitor Silva","family":"Pereira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0255-5889","authenticated-orcid":false,"given":"S\u00e2mia R.L.","family":"Joca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9864-7894","authenticated-orcid":false,"given":"Brian H.","family":"Harvey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6939-5088","authenticated-orcid":false,"given":"Betina","family":"Elfving","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0081-0068","authenticated-orcid":false,"given":"Gregers","family":"Wegener","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2019,6,24]]},"reference":[{"key":"S0924270819000255_ref39","doi-asserted-by":"publisher","DOI":"10.1126\/science.1190287"},{"key":"S0924270819000255_ref38","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.31.246"},{"key":"S0924270819000255_ref9","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2006.06.033"},{"key":"S0924270819000255_ref69","doi-asserted-by":"publisher","DOI":"10.3389\/fpsyt.2015.00172"},{"key":"S0924270819000255_ref37","doi-asserted-by":"publisher","DOI":"10.1016\/S0091-3057(01)00625-6"},{"key":"S0924270819000255_ref8","doi-asserted-by":"publisher","DOI":"10.1038\/nature10130"},{"key":"S0924270819000255_ref68","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3956(00)00016-9"},{"key":"S0924270819000255_ref7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2006.07.007"},{"key":"S0924270819000255_ref36","doi-asserted-by":"publisher","DOI":"10.4103\/0976-500X.72351"},{"key":"S0924270819000255_ref67","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2016.12.070"},{"key":"S0924270819000255_ref6","first-page":"247","volume":"20","author":"Ardalan","year":"2017","journal-title":"The International Journal of Neuropsychopharmacology"},{"key":"S0924270819000255_ref35","doi-asserted-by":"publisher","DOI":"10.1001\/jama.289.23.3095"},{"key":"S0924270819000255_ref66","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.63.8.856"},{"key":"S0924270819000255_ref5","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13714"},{"key":"S0924270819000255_ref34","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2010.05.007"},{"key":"S0924270819000255_ref65","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.12223"},{"key":"S0924270819000255_ref4","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.22617"},{"key":"S0924270819000255_ref33","doi-asserted-by":"publisher","DOI":"10.1016\/0165-1781(83)90062-8"},{"key":"S0924270819000255_ref64","doi-asserted-by":"publisher","DOI":"10.1038\/nature17998"},{"key":"S0924270819000255_ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2005.09.008"},{"key":"S0924270819000255_ref32","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-006-0326-2"},{"key":"S0924270819000255_ref63","doi-asserted-by":"publisher","DOI":"10.1016\/j.psyneuen.2004.02.002"},{"key":"S0924270819000255_ref2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2015.05.018"},{"key":"S0924270819000255_ref31","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.749"},{"key":"S0924270819000255_ref62","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-016-4399-2"},{"key":"S0924270819000255_ref1","doi-asserted-by":"publisher","DOI":"10.1016\/0031-9384(90)90306-O"},{"key":"S0924270819000255_ref30","doi-asserted-by":"publisher","DOI":"10.1016\/S0924-9338(02)00653-3"},{"key":"S0924270819000255_ref61","volume-title":"Depression \u2013Fact Sheet","year":"2018"},{"key":"S0924270819000255_ref60","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-015-4034-7"},{"key":"S0924270819000255_ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.cobeha.2016.09.012"},{"key":"S0924270819000255_ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2015.07.015"},{"key":"S0924270819000255_ref59","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2015.07.026"},{"key":"S0924270819000255_ref58","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.12.033"},{"key":"S0924270819000255_ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.05.024"},{"key":"S0924270819000255_ref57","first-page":"222","volume":"26","author":"Trevino","year":"2014","journal-title":"Annals of Clinical Psychiatry"},{"key":"S0924270819000255_ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.05.029"},{"key":"S0924270819000255_ref56","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.09.032"},{"key":"S0924270819000255_ref24","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-016-4327-5"},{"key":"S0924270819000255_ref55","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2017.09.029"},{"key":"S0924270819000255_ref23","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00978"},{"key":"S0924270819000255_ref54","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2014.261"},{"key":"S0924270819000255_ref22","doi-asserted-by":"publisher","DOI":"10.1001\/jamapsychiatry.2017.3739"},{"key":"S0924270819000255_ref53","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2011.02.017"},{"key":"S0924270819000255_ref21","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291709005558"},{"key":"S0924270819000255_ref52","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01489.x"},{"key":"S0924270819000255_ref20","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2018.17060720"},{"key":"S0924270819000255_ref51","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2019.1559295"},{"key":"S0924270819000255_ref50","first-page":"13","volume":"34","author":"Quarton","year":"1955","journal-title":"Medicine (United States)"},{"key":"S0924270819000255_ref19","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.09.004"},{"key":"S0924270819000255_ref18","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2012.246"},{"key":"S0924270819000255_ref49","doi-asserted-by":"publisher","DOI":"10.1038\/266730a0"},{"key":"S0924270819000255_ref17","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2009.04.012"},{"key":"S0924270819000255_ref48","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-014-3853-2"},{"key":"S0924270819000255_ref16","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2015.07.039"},{"key":"S0924270819000255_ref47","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(02)00653-0"},{"key":"S0924270819000255_ref15","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2013.00161"},{"key":"S0924270819000255_ref14","doi-asserted-by":"publisher","DOI":"10.1017\/neu.2016.50"},{"key":"S0924270819000255_ref45","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X14666160321122703"},{"key":"S0924270819000255_ref13","doi-asserted-by":"publisher","DOI":"10.1017\/neu.2016.44"},{"key":"S0924270819000255_ref44","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1314.001"},{"key":"S0924270819000255_ref12","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3223(99)00230-9"},{"key":"S0924270819000255_ref43","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291798006680"},{"key":"S0924270819000255_ref11","doi-asserted-by":"publisher","DOI":"10.5127\/pr.034413"},{"key":"S0924270819000255_ref42","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.02.010"},{"key":"S0924270819000255_ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychires.2014.07.027"},{"key":"S0924270819000255_ref41","doi-asserted-by":"publisher","DOI":"10.1017\/neu.2014.39"},{"key":"S0924270819000255_ref40","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.12.015"}],"container-title":["Acta Neuropsychiatrica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0924270819000255","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,16]],"date-time":"2019-09-16T04:21:41Z","timestamp":1568607701000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0924270819000255\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,24]]},"references-count":67,"journal-issue":{"issue":"05","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["S0924270819000255"],"URL":"https:\/\/doi.org\/10.1017\/neu.2019.25","relation":{},"ISSN":["0924-2708","1601-5215"],"issn-type":[{"value":"0924-2708","type":"print"},{"value":"1601-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,24]]},"assertion":[{"value":"\u00a9 Scandinavian College of Neuropsychopharmacology 2019\u00a0This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http:\/\/creativecommons.org\/licenses\/by\/4.0\/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}}]}}