{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T12:37:51Z","timestamp":1793968671116,"version":"4.8.0"},"reference-count":42,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["T32 MH014677"],"award-info":[{"award-number":["T32 MH014677"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","jns-journal.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Journal of the Neurological Sciences"],"published-print":{"date-parts":[[2022,3]]},"DOI":"10.1016\/j.jns.2021.120092","type":"journal-article","created":{"date-parts":[[2021,12,15]],"date-time":"2021-12-15T21:01:36Z","timestamp":1639602096000},"page":"120092","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":14,"special_numbering":"C","title":["Nitrous Oxide: an emerging novel treatment for treatment-resistant depression"],"prefix":"10.1016","volume":"434","author":[{"given":"Darin F.","family":"Quach","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria C.","family":"de Leon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles R.","family":"Conway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.jns.2021.120092_bb0005","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1001\/archpsyc.1994.03950110025005","article-title":"Serotonin and the neurobiology of depression","volume":"51","author":"Delgado","year":"1994","journal-title":"Arch. Gen. Psychiatry"},{"key":"10.1016\/j.jns.2021.120092_bb0010","first-page":"4","article-title":"History and evolution of the monoamine hypothesis of depression","volume":"61","author":"Hirschfeld Robert","year":"2000","journal-title":"J. Clin. Psychiatry."},{"key":"10.1016\/j.jns.2021.120092_bb0015","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1176\/ajp.122.5.509","article-title":"The catecholamine hypothesis of affective disorders: a review of supporting evidence","volume":"122","author":"Schildkraut","year":"1965","journal-title":"Am. J. Psychiatr."},{"key":"10.1016\/j.jns.2021.120092_bb0020","first-page":"7","article-title":"Depression: the case for a monoamine deficiency","volume":"61","author":"Delgado Pedro","year":"2000","journal-title":"J. Clin. Psychiatry."},{"key":"10.1016\/j.jns.2021.120092_bb0025","first-page":"1905","article-title":"STAR-D (2006; AjPsych) Tiered approach for depression","volume":"16311","author":"John Rush","year":"2006","journal-title":"Am. J. Psychiatry"},{"key":"10.1016\/j.jns.2021.120092_bb0030","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1001\/jamapsychiatry.2016.2586","article-title":"Toward an evidence-based, operational definition of treatment-resistant depression: when enough is enough","volume":"74","author":"Conway","year":"2017","journal-title":"JAMA Psychiatry."},{"key":"10.1016\/j.jns.2021.120092_bb0035","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1002\/da.22968","article-title":"Defining treatment-resistant depression","volume":"37","author":"Gaynes","year":"2020","journal-title":"Depress. Anxiety"},{"key":"10.1016\/j.jns.2021.120092_bb0040","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1037\/pha0000084","article-title":"Clinical applications of hallucinogens: a review","volume":"24","author":"Garcia-Romeu","year":"2016","journal-title":"Exp. Clin. Psychopharmacol."},{"key":"10.1016\/j.jns.2021.120092_bb0045","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s12264-015-0009-2","article-title":"Therapeutic efficacy of neurostimulation for depression: techniques, current modalities, and future challenges","volume":"32","author":"Akhtar","year":"2016","journal-title":"Neurosci. Bull."},{"key":"10.1016\/j.jns.2021.120092_bb0050","doi-asserted-by":"crossref","DOI":"10.1016\/j.ynstr.2019.100196","article-title":"Neurosteroids as novel antidepressants and anxiolytics: GABA-A receptors and beyond","volume":"11","author":"Zorumski","year":"2019","journal-title":"Neurobiol. Stress."},{"key":"10.1016\/j.jns.2021.120092_bb0055","doi-asserted-by":"crossref","first-page":"336","DOI":"10.1016\/j.neubiorev.2014.08.017","article-title":"The role of NMDA receptors in the pathophysiology and treatment of mood disorders","volume":"47","author":"Ghasemi","year":"2014","journal-title":"Neurosci. Biobehav. Rev."},{"key":"10.1016\/j.jns.2021.120092_bb0060","doi-asserted-by":"crossref","first-page":"124","DOI":"10.2344\/0003-3006-55.4.124","article-title":"Nitrous oxide and the inhalation anesthetics","volume":"55","author":"Becker","year":"2008","journal-title":"Anesth. Prog."},{"key":"10.1016\/j.jns.2021.120092_bb0065","series-title":"Safety of Inhalation of a 50% Nitrous Oxide\/Oxygen Premix a Prospective Survey of 35 828 Administrations","author":"Onody","year":"2006"},{"key":"10.1016\/j.jns.2021.120092_bb0070","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1097\/JCP.0000000000000837","article-title":"Exploring nitrous oxide as treatment of mood disorders: basic concepts","volume":"38","author":"Nagele","year":"2018","journal-title":"J. Clin. Psychopharmacol."},{"key":"10.1016\/j.jns.2021.120092_bb0075","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.clineuro.2018.08.016","article-title":"Subacute combined degeneration of the spinal cord following nitrous oxide anesthesia: a systematic review of cases","volume":"173","author":"Patel","year":"2018","journal-title":"Clin. Neurol. Neurosurg."},{"key":"10.1016\/j.jns.2021.120092_bb0080","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.biopsych.2014.11.016","article-title":"Nitrous oxide for treatment-resistant major depression: a proof-of-concept trial","volume":"78","author":"Nagele","year":"2015","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.jns.2021.120092_bb0085","author":"Nagele"},{"key":"10.1016\/j.jns.2021.120092_bb0090","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1590\/1516-4446-2020-1543","article-title":"Nitrous oxide as an adjunctive therapy in major depressive disorder: a randomized controlled double-blind pilot trial","volume":"43","author":"Guimar\u00e3es","year":"2021","journal-title":"Braz. J. Psychiatry."},{"key":"10.1016\/j.jns.2021.120092_bb0095","doi-asserted-by":"crossref","first-page":"8791","DOI":"10.1073\/pnas.0402825101","article-title":"Nitrous oxide (N2O) requires the N-methyl-D-aspartate receptor for its action in Caenorhabditis elegans","volume":"101","author":"Nagele","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"10.1016\/j.jns.2021.120092_bb0100","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1097\/00000542-200503000-00013","article-title":"Effect of N-methyl-D-aspartate receptor \u03b51 subunit gene disruption of the action of general anesthetic drugs in mice","volume":"102","author":"Sato","year":"2005","journal-title":"Anesthesiology."},{"key":"10.1016\/j.jns.2021.120092_bb0105","doi-asserted-by":"crossref","first-page":"9716","DOI":"10.1523\/JNEUROSCI.18-23-09716.1998","article-title":"Effect of nitrous oxide on excitatory and inhibitory synaptic transmission in hippocampal cultures","volume":"18","author":"Mennerick","year":"1998","journal-title":"J. Neurosci."},{"key":"10.1016\/j.jns.2021.120092_bb0110","doi-asserted-by":"crossref","first-page":"8688","DOI":"10.1523\/JNEUROSCI.6078-08.2009","article-title":"Positive AMPA receptor modulation rapidly stimulates BDNF release and increases dendritic mRNA translation","volume":"29","author":"Jourdi","year":"2009","journal-title":"J. Neurosci."},{"key":"10.1016\/j.jns.2021.120092_bb0115","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-020-58017-3","article-title":"AMPA receptor-mTORC1 signaling activation is required for neuroplastic effects of LY341495 in rat hippocampal neurons","volume":"10","author":"Seo","year":"2020","journal-title":"Sci. Rep."},{"key":"10.1016\/j.jns.2021.120092_bb0120","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nature17998","article-title":"NMDAR inhibition-independent antidepressant actions of ketamine metabolites","volume":"533","author":"Zanos","year":"2016","journal-title":"Nature."},{"key":"10.1016\/j.jns.2021.120092_bb0125","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1038\/npp.2016.184","article-title":"Temporal dynamics of antidepressant ketamine effects on glutamine cycling follow regional fingerprints of AMPA and NMDA receptor densities","volume":"42","author":"Li","year":"2017","journal-title":"Neuropsychopharmacology."},{"key":"10.1016\/j.jns.2021.120092_bb0130","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/s00540-010-0886-5","article-title":"Involvement of the \u03ba-opioid receptor in nitrous oxide-induced analgesia in mice","volume":"24","author":"Koyama","year":"2010","journal-title":"J. Anesth."},{"key":"10.1016\/j.jns.2021.120092_bb0135","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1385\/MN:25:2:167","article-title":"Neurobiology of nitrous oxide-induced antinociceptive effects","volume":"25","author":"Fujinaga","year":"2002","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.jns.2021.120092_bb0140","doi-asserted-by":"crossref","first-page":"2344","DOI":"10.1038\/npp.2016.38","article-title":"Antidepressant-like effects of buprenorphine are mediated by kappa opioid receptors","volume":"41","author":"Falcon","year":"2016","journal-title":"Neuropsychopharmacology."},{"key":"10.1016\/j.jns.2021.120092_bb0145","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1176\/appi.ajp.2018.18020138","article-title":"Attenuation of antidepressant effects of ketamine by opioid receptor antagonism","volume":"175","author":"Williams","year":"2018","journal-title":"Am. J. Psychiatr."},{"key":"10.1016\/j.jns.2021.120092_bb0150","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1111\/j.1476-5381.1996.tb15430.x","article-title":"Effects of inhalational general anaesthetics on native glycine receptors in rat medullary neurones and recombinant glycine receptors in Xenopus oocytes","volume":"118","author":"Downie","year":"1996","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.jns.2021.120092_bb0155","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/S0378-4274(98)00167-2","article-title":"Post-synaptic inhibitory mechanisms of anaesthesia; glycine receptors","volume":"100\u2013101","author":"Daniels","year":"1998","journal-title":"Toxicol. Lett."},{"key":"10.1016\/j.jns.2021.120092_bb0160","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S0026-895X(24)12624-7","article-title":"Cav3.2 Channel is a molecular substrate for inhibition of T-type calcium currents in rat sensory neurons by nitrous oxide","volume":"60","author":"Todorovic","year":"2001","journal-title":"Mol. Pharmacol."},{"key":"10.1016\/j.jns.2021.120092_bb0165","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1111\/j.1749-6632.1991.tb33886.x","article-title":"Effects of chronic exposure to nitrous oxide on membrane fluidity in rats","volume":"625","author":"Frank","year":"1991","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.jns.2021.120092_bb0170","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.clinph.2012.08.007","article-title":"Effects of nitrous oxide sedation on resting electroencephalogram topography","volume":"124","author":"Foster","year":"2013","journal-title":"Clin. Neurophysiol."},{"key":"10.1016\/j.jns.2021.120092_bb0175","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/j.clinph.2015.06.001","article-title":"Nitrous oxide-induced slow and delta oscillations","volume":"127","author":"Pavone","year":"2016","journal-title":"Clin. Neurophysiol."},{"key":"10.1016\/j.jns.2021.120092_bb0180","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nrn3504","article-title":"NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease","volume":"14","author":"Paoletti","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.jns.2021.120092_bb0185","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1124\/pr.109.002451","article-title":"Glutamate receptor ion channels: structure, regulation, and function","volume":"62","author":"Traynelis","year":"2010","journal-title":"Pharmacol. Rev."},{"key":"10.1016\/j.jns.2021.120092_bb0190","series-title":"Block of N-Methyl-D-Aspartate-Activated Current by the Anticonvulsant MK-801: Selective Binding to Open Channels (Excitatory Amino Acid Receptors\/Visual Cortex\/Cell Culture\/Single Channels)","author":"Huettner","year":"1988"},{"key":"10.1016\/j.jns.2021.120092_bb0195","doi-asserted-by":"crossref","first-page":"4589","DOI":"10.1113\/jphysiol.2009.176297","article-title":"Memantine binding to a superficial site on NMDA receptors contributes to partial trapping","volume":"587","author":"Kotermanski","year":"2009","journal-title":"J. Physiol."},{"key":"10.1016\/j.jns.2021.120092_bb0200","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1017\/S003329171600026X","article-title":"Nitrous oxide speeds the reduction of distressing intrusive memories in an experimental model of psychological trauma","volume":"46","author":"Das","year":"2016","journal-title":"Psychol. Med."},{"key":"10.1016\/j.jns.2021.120092_bb0205","doi-asserted-by":"crossref","DOI":"10.1016\/j.conctc.2020.100600","article-title":"Nitrous oxide as a putative novel dual-mechanism treatment for bipolar depression: proof-of-concept study design and methodology","volume":"19","author":"Dimick","year":"2020","journal-title":"Contemp. Clin. Trials Commun."},{"key":"10.1016\/j.jns.2021.120092_bb0210","doi-asserted-by":"crossref","DOI":"10.1016\/j.ypmed.2021.106524","article-title":"The rapid anti-suicidal ideation effect of ketamine: a systematic review","volume":"152","author":"Hochschild","year":"2021","journal-title":"Prev. Med."}],"container-title":["Journal of the Neurological Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022510X21027945?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0022510X21027945?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T15:58:13Z","timestamp":1758383893000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0022510X21027945"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3]]},"references-count":42,"alternative-id":["S0022510X21027945"],"URL":"https:\/\/doi.org\/10.1016\/j.jns.2021.120092","relation":{},"ISSN":["0022-510X"],"issn-type":[{"value":"0022-510X","type":"print"}],"subject":[],"published":{"date-parts":[[2022,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Nitrous Oxide: an emerging novel treatment for treatment-resistant depression","name":"articletitle","label":"Article Title"},{"value":"Journal of the Neurological Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.jns.2021.120092","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"120092"}}