{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:43:28Z","timestamp":1790739808578,"version":"4.1.0"},"reference-count":120,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Behavioural Brain Research"],"published-print":{"date-parts":[[2020,4]]},"DOI":"10.1016\/j.bbr.2020.112532","type":"journal-article","created":{"date-parts":[[2020,2,2]],"date-time":"2020-02-02T09:14:41Z","timestamp":1580634881000},"page":"112532","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":16,"special_numbering":"C","title":["Ketamine: Leading us into the future for development of antidepressants"],"prefix":"10.1016","volume":"383","author":[{"given":"Flavia R.","family":"Carreno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Lodge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Frazer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"1-2","key":"10.1016\/j.bbr.2020.112532_bib0005","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.jad.2008.10.014","article-title":"What happens to patients with treatment-resistant depression? A systematic review of medium to long term outcome studies","volume":"116","author":"Fekadu","year":"2009","journal-title":"J. Affect. Disorders"},{"issue":"9","key":"10.1016\/j.bbr.2020.112532_bib0010","doi-asserted-by":"crossref","first-page":"1997","DOI":"10.1017\/S0033291712000025","article-title":"Lifetime co-morbidity of DSM-IV disorders in the US national comorbidity survey replication adolescent supplement (NCS-A)","volume":"42","author":"Kessler","year":"2012","journal-title":"Psychol. Med."},{"issue":"8","key":"10.1016\/j.bbr.2020.112532_bib0015","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1176\/appi.ps.201300059","article-title":"A review of the clinical, economic, and societal burden of treatment-resistant depression: 1996-2013","volume":"65","author":"Mrazek","year":"2014","journal-title":"Psychiatr. Serv."},{"issue":"Suppl 10","key":"10.1016\/j.bbr.2020.112532_bib0020","first-page":"8","article-title":"Limitations in efficacy of antidepressant monotherapy","volume":"68","author":"Rush","year":"2007","journal-title":"J. Clin. Psychiatry"},{"issue":"3","key":"10.1016\/j.bbr.2020.112532_bib0025","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/sj.npp.1300341","article-title":"Onset and early behavioral effects of pharmacologically different antidepressants and placebo in depression","volume":"29","author":"Katz","year":"2004","journal-title":"Neuropsychopharmacology"},{"issue":"2","key":"10.1016\/j.bbr.2020.112532_bib0030","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/0924-977X(93)90264-M","article-title":"Time course of improvement under antidepressant treatment: a survival-analytical approach","volume":"3","author":"Stassen","year":"1993","journal-title":"Eur. Neuropsychopharmacol."},{"issue":"2","key":"10.1016\/j.bbr.2020.112532_bib0035","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1192\/bjp.bp.111.096594","article-title":"Putting the efficacy of psychiatric and general medicine medication into perspective: review of meta-analyses","volume":"200","author":"Leucht","year":"2012","journal-title":"Br. J. Psychiatry"},{"issue":"2","key":"10.1016\/j.bbr.2020.112532_bib0040","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1093\/ijnp\/pyy052","article-title":"The impact of (the concept of) treatment-resistant depression: an opinion review","volume":"22","author":"Demyttenaere","year":"2019","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"10.1016\/j.bbr.2020.112532_bib0045","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jad.2013.10.043","article-title":"Treatment-resistant depression: definitions, review of the evidence, and algorithmic approach","volume":"156","author":"McIntyre","year":"2014","journal-title":"J. Affect. Disord."},{"key":"10.1016\/j.bbr.2020.112532_bib0050","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.jpsychires.2019.03.021","article-title":"The assessment of resistance to antidepressant treatment: rationale for the Antidepressant Treatment History Form: short Form (ATHF-SF)","volume":"113","author":"Sackeim","year":"2019","journal-title":"J. Psychiatr. Res."},{"key":"10.1016\/j.bbr.2020.112532_bib0055","doi-asserted-by":"crossref","DOI":"10.12688\/f1000research.6633.1","article-title":"Update on neuromodulation for treatment-resistant depression","volume":"4","author":"Bewernick","year":"2015","journal-title":"F1000Research"},{"issue":"3","key":"10.1016\/j.bbr.2020.112532_bib0060","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1007\/s13311-017-0537-8","article-title":"Vagal nerve stimulation for treatment-resistant depression","volume":"14","author":"Carreno","year":"2017","journal-title":"Neurotherapeutics"},{"key":"10.1016\/j.bbr.2020.112532_bib0065","article-title":"Vagus nerve stimulation in psychiatry: a systematic review of the available evidence","author":"Cimpianu","year":"2016","journal-title":"J. Neural Transm. Vienna"},{"issue":"1-2","key":"10.1016\/j.bbr.2020.112532_bib0070","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0014-2999(94)90516-9","article-title":"Antidepressant activity of non-competitive and competitive NMDA receptor antagonists in a chronic mild stress model of depression","volume":"263","author":"Papp","year":"1994","journal-title":"Eur. J. Pharmacol."},{"issue":"12","key":"10.1016\/j.bbr.2020.112532_bib0075","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1016\/j.biopsych.2013.01.021","article-title":"Glutamate-based antidepressants: preclinical psychopharmacology","volume":"73","author":"Pilc","year":"2013","journal-title":"Biol. Psychiatry"},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0080","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0014-2999(90)90204-J","article-title":"Functional antagonists at the NMDA receptor complex exhibit antidepressant actions","volume":"185","author":"Trullas","year":"1990","journal-title":"Eur. J. Pharmacol."},{"issue":"4","key":"10.1016\/j.bbr.2020.112532_bib0085","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/S0006-3223(99)00230-9","article-title":"Antidepressant effects of ketamine in depressed patients","volume":"47","author":"Berman","year":"2000","journal-title":"Biol. Psychiatry"},{"issue":"4","key":"10.1016\/j.bbr.2020.112532_bib0090","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/j.biopsych.2012.06.022","article-title":"Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression","volume":"74","author":"Murrough","year":"2013","journal-title":"Biol. Psychiatry"},{"issue":"8","key":"10.1016\/j.bbr.2020.112532_bib0095","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1176\/appi.ajp.2016.16010037","article-title":"Randomized, placebo-controlled, dose-frequency study of intravenous ketamine in patients with treatment-resistant depression","volume":"173","author":"Singh","year":"2016","journal-title":"Am. J. Psychiatry"},{"issue":"8","key":"10.1016\/j.bbr.2020.112532_bib0100","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1001\/archpsyc.63.8.856","article-title":"A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression","volume":"63","author":"Zarate","year":"2006","journal-title":"Arch. Gen. Psychiatry"},{"issue":"5","key":"10.1016\/j.bbr.2020.112532_bib0105","doi-asserted-by":"crossref","first-page":"596","DOI":"10.1177\/0269881114568041","article-title":"Neural correlates of change in major depressive disorder anhedonia following open-label ketamine","volume":"29","author":"Lally","year":"2015","journal-title":"J. Psychopharmacol."},{"key":"10.1016\/j.bbr.2020.112532_bib0110","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.jpsychires.2014.07.027","article-title":"Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety","volume":"58","author":"Ballard","year":"2014","journal-title":"J. Psychiatr. Res."},{"issue":"16","key":"10.1016\/j.bbr.2020.112532_bib0115","doi-asserted-by":"crossref","first-page":"3571","DOI":"10.1017\/S0033291715001506","article-title":"Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial","volume":"45","author":"Murrough","year":"2015","journal-title":"Psychol. Med."},{"issue":"4","key":"10.1016\/j.bbr.2020.112532_bib0120","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1002\/da.22253","article-title":"Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression","volume":"31","author":"Price","year":"2014","journal-title":"Depress. Anxiety"},{"issue":"7354","key":"10.1016\/j.bbr.2020.112532_bib0125","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nature10130","article-title":"NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses","volume":"475","author":"Autry","year":"2011","journal-title":"Nature"},{"issue":"9","key":"10.1016\/j.bbr.2020.112532_bib0130","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1038\/mp.2015.176","article-title":"Activation of a ventral hippocampus-medial prefrontal cortex pathway is both necessary and sufficient for an antidepressant response to ketamine","volume":"21","author":"Carreno","year":"2016","journal-title":"Mol. Psychiatry"},{"issue":"8","key":"10.1016\/j.bbr.2020.112532_bib0135","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1016\/j.biopsych.2010.12.015","article-title":"Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure","volume":"69","author":"Li","year":"2011","journal-title":"Biol. Psychiatry"},{"issue":"5","key":"10.1016\/j.bbr.2020.112532_bib0140","first-page":"567","article-title":"Pharmacokinetics of ketamine and xylazine in young and old Sprague-Dawley rats","volume":"52","author":"Veilleux-Lemieux","year":"2013","journal-title":"J. Am. Assoc. Lab. Anim. Sci."},{"issue":"4","key":"10.1016\/j.bbr.2020.112532_bib0145","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.biopsych.2007.05.028","article-title":"Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors","volume":"63","author":"Maeng","year":"2008","journal-title":"Biol. Psychiatry"},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0150","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.neuropharm.2011.08.044","article-title":"Signaling pathways underlying the rapid antidepressant actions of ketamine","volume":"62","author":"Duman","year":"2012","journal-title":"Neuropharmacology"},{"issue":"3","key":"10.1016\/j.bbr.2020.112532_bib0155","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nm.4050","article-title":"Synaptic plasticity and depression: new insights from stress and rapid-acting antidepressants","volume":"22","author":"Duman","year":"2016","journal-title":"Nat. Med."},{"key":"10.1016\/j.bbr.2020.112532_bib0160","doi-asserted-by":"crossref","DOI":"10.1155\/2016\/8056370","article-title":"Dendritic spines in depression: what we learned from animal models","volume":"2016","author":"Qiao","year":"2016","journal-title":"Neural Plast."},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0165","doi-asserted-by":"crossref","first-page":"71","DOI":"10.2174\/1570159X14666160202121111","article-title":"Synaptic plasticity, metaplasticity and depression","volume":"15","author":"Vose","year":"2017","journal-title":"Curr. Neuropharmacol."},{"issue":"6436","key":"10.1016\/j.bbr.2020.112532_bib0170","doi-asserted-by":"crossref","DOI":"10.1126\/science.aat8078","article-title":"Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation","volume":"364","author":"Moda-Sava","year":"2019","journal-title":"Science"},{"key":"10.1016\/j.bbr.2020.112532_bib0175","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.cobeha.2018.02.001","article-title":"Sex differences in sub-anesthetic ketamine\u2019s antidepressant effects and abuse liability","volume":"23","author":"Wright","year":"2018","journal-title":"Curr. Opin. Behav. Sci."},{"key":"10.1016\/j.bbr.2020.112532_bib0180","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.neuropharm.2012.12.009","article-title":"Sex differences in the antidepressant-like effects of ketamine","volume":"70","author":"Carrier","year":"2013","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.bbr.2020.112532_bib0185","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neuroscience.2015.01.008","article-title":"Sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naive and \"depressed\" mice exposed to chronic mild stress","volume":"290","author":"Franceschelli","year":"2015","journal-title":"Neuroscience"},{"key":"10.1016\/j.bbr.2020.112532_bib0190","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.bbr.2016.06.041","article-title":"Repeated ketamine treatment induces sex-specific behavioral and neurochemical effects in mice","volume":"312","author":"Thelen","year":"2016","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.bbr.2020.112532_bib0195","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.jpsychires.2019.01.010","article-title":"Sex differences in response to ketamine as a rapidly acting intervention for treatment resistant depression","volume":"110","author":"Freeman","year":"2019","journal-title":"J. Psychiatr. Res."},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0200","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1097\/00000542-199801000-00015","article-title":"Psychedelic effects of ketamine in healthy volunteers: relationship to steady-state plasma concentrations","volume":"88","author":"Bowdle","year":"1998","journal-title":"Anesthesiology"},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0205","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S2215-0366(17)30272-9","article-title":"Side-effects associated with ketamine use in depression: a systematic review","volume":"5","author":"Short","year":"2018","journal-title":"Lancet Psychiatry"},{"key":"10.1016\/j.bbr.2020.112532_bib0210","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbr.2019.111928","article-title":"Long-lasting effects of repeated ketamine administration in adult and adolescent rats","volume":"369","author":"Bates","year":"2019","journal-title":"Behav. Brain Res."},{"issue":"3","key":"10.1016\/j.bbr.2020.112532_bib0215","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1093\/ilar.52.3.366","article-title":"The neurobehavioral pharmacology of ketamine: implications for drug abuse, addiction, and psychiatric disorders, ILAR journal \/ National Research Council","volume":"52","author":"Trujillo","year":"2011","journal-title":"Inst. Lab. Anim. Resour."},{"issue":"2","key":"10.1016\/j.bbr.2020.112532_bib0220","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1001\/jamapsychiatry.2017.3739","article-title":"Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial","volume":"75","author":"Daly","year":"2018","journal-title":"JAMA Psychiatry"},{"issue":"6","key":"10.1016\/j.bbr.2020.112532_bib0225","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1176\/appi.ajp.2019.19020172","article-title":"Efficacy and safety of flexibly dosed esketamine nasal spray combined with a newly initiated oral antidepressant in treatment-resistant depression: a randomized double-blind active-controlled study","volume":"176","author":"Popova","year":"2019","journal-title":"Am. J. Psychiatry"},{"issue":"2","key":"10.1016\/j.bbr.2020.112532_bib0230","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1111\/acps.13063","article-title":"Promises and concerns regarding the use of ketamine and esketamine in the treatment of depression","volume":"140","author":"Perez-Esparza","year":"2019","journal-title":"Acta Psychiatr. Scand."},{"issue":"6","key":"10.1016\/j.bbr.2020.112532_bib0235","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1176\/appi.ajp.2019.19040423","article-title":"A word to the wise about intranasal Esketamine","volume":"176","author":"Schatzberg","year":"2019","journal-title":"Am. J. Psychiatry"},{"key":"10.1016\/j.bbr.2020.112532_bib0240","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.pbb.2013.11.033","article-title":"R (-)-ketamine shows greater potency and longer lasting antidepressant effects than S (+)-ketamine","volume":"116","author":"Zhang","year":"2014","journal-title":"Pharmacol. Biochem. Behav."},{"key":"10.1016\/j.bbr.2020.112532_bib0245","doi-asserted-by":"crossref","first-page":"e632","DOI":"10.1038\/tp.2015.136","article-title":"R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects","volume":"5","author":"Yang","year":"2015","journal-title":"Transl. Psychiatry"},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0250","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.biopsych.2017.10.026","article-title":"Intracellular signaling pathways involved in (S)- and (R)-Ketamine antidepressant actions","volume":"83","author":"Zanos","year":"2018","journal-title":"Biol. Psychiatry"},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0255","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1080\/14737175.2019.1554434","article-title":"An update on ketamine and its two enantiomers as rapid-acting antidepressants","volume":"19","author":"Zhang","year":"2019","journal-title":"Expert Rev. Neurother."},{"issue":"6","key":"10.1016\/j.bbr.2020.112532_bib0260","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1176\/ajp.154.6.805","article-title":"Association of ketamine-induced psychosis with focal activation of the prefrontal cortex in healthy volunteers","volume":"154","author":"Breier","year":"1997","journal-title":"Am. J. Psychiatry"},{"issue":"6","key":"10.1016\/j.bbr.2020.112532_bib0265","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1097\/00001756-199504190-00011","article-title":"Ketamine activates psychosis and alters limbic blood flow in schizophrenia","volume":"6","author":"Lahti","year":"1995","journal-title":"Neuroreport"},{"issue":"3","key":"10.1016\/j.bbr.2020.112532_bib0270","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1016\/S0306-4522(02)00298-1","article-title":"Acute administration of phencyclidine induces tonic activation of medial prefrontal cortex neurons in freely moving rats","volume":"114","author":"Suzuki","year":"2002","journal-title":"Neuroscience"},{"issue":"5","key":"10.1016\/j.bbr.2020.112532_bib0275","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/S0893-133X(96)00246-1","article-title":"Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis","volume":"16","author":"Vollenweider","year":"1997","journal-title":"Neuropsychopharmacology"},{"issue":"8","key":"10.1016\/j.bbr.2020.112532_bib0280","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1523\/JNEUROSCI.17-08-02921.1997","article-title":"Activation of glutamatergic neurotransmission by ketamine: a novel step in the pathway from NMDA receptor blockade to dopaminergic and cognitive disruptions associated with the prefrontal cortex","volume":"17","author":"Moghaddam","year":"1997","journal-title":"J. Neurosci."},{"issue":"22","key":"10.1016\/j.bbr.2020.112532_bib0285","doi-asserted-by":"crossref","first-page":"8467","DOI":"10.1073\/pnas.0308455101","article-title":"NMDA receptor hypofunction produces concomitant firing rate potentiation and burst activity reduction in the prefrontal cortex","volume":"101","author":"Jackson","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"43","key":"10.1016\/j.bbr.2020.112532_bib0290","doi-asserted-by":"crossref","first-page":"11496","DOI":"10.1523\/JNEUROSCI.2213-07.2007","article-title":"NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons","volume":"27","author":"Homayoun","year":"2007","journal-title":"J. Neurosci."},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0295","doi-asserted-by":"crossref","first-page":"11","DOI":"10.31887\/DCNS.2014.16.1\/rduman","article-title":"Pathophysiology of depression and innovative treatments: remodeling glutamatergic synaptic connections","volume":"16","author":"Duman","year":"2014","journal-title":"Dialogues Clin. Neurosci."},{"issue":"13","key":"10.1016\/j.bbr.2020.112532_bib0300","doi-asserted-by":"crossref","first-page":"E3007","DOI":"10.1073\/pnas.1718883115","article-title":"Disinhibition of CA1 pyramidal cells by low-dose ketamine and other antagonists with rapid antidepressant efficacy","volume":"115","author":"Widman","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"7604","key":"10.1016\/j.bbr.2020.112532_bib0305","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"},{"issue":"9","key":"10.1016\/j.bbr.2020.112532_bib0310","doi-asserted-by":"crossref","first-page":"1900","DOI":"10.1038\/s41386-018-0084-y","article-title":"(2R,6R)-Hydroxynorketamine is not essential for the antidepressant actions of (R)-ketamine in mice","volume":"43","author":"Yamaguchi","year":"2018","journal-title":"Neuropsychopharmacology"},{"issue":"12","key":"10.1016\/j.bbr.2020.112532_bib0315","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. Psychiatry"},{"issue":"9","key":"10.1016\/j.bbr.2020.112532_bib0320","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/0028-3908(87)90084-0","article-title":"Properties of the interaction between ketamine and opiate binding sites in vivo and in vitro","volume":"26","author":"Smith","year":"1987","journal-title":"Neuropharmacology"},{"issue":"3","key":"10.1016\/j.bbr.2020.112532_bib0325","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/0014-2999(89)90339-7","article-title":"[3H]MK-801 binding sites in post-mortem human frontal cortex","volume":"162","author":"Kornhuber","year":"1989","journal-title":"Eur. J. Pharmacol."},{"issue":"3","key":"10.1016\/j.bbr.2020.112532_bib0330","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1124\/pr.117.015198","article-title":"Ketamine and ketamine metabolite pharmacology: insights into therapeutic mechanisms","volume":"70","author":"Zanos","year":"2018","journal-title":"Pharmacol. Rev."},{"issue":"3","key":"10.1016\/j.bbr.2020.112532_bib0335","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1001\/jamapsychiatry.2018.3990","article-title":"Association of combined naltrexone and ketamine with depressive symptoms in a case series of patients with depression and alcohol use disorder","volume":"76","author":"Yoon","year":"2019","journal-title":"JAMA Psychiatry"},{"issue":"6","key":"10.1016\/j.bbr.2020.112532_bib0340","doi-asserted-by":"crossref","first-page":"e25","DOI":"10.1016\/j.biopsych.2018.11.006","article-title":"Lack of opioid system in the antidepressant actions of ketamine","volume":"85","author":"Zhang","year":"2019","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.bbr.2020.112532_bib0345","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1916570117","article-title":"Opioid system is necessary but not sufficient for antidepressive actions of ketamine in rodents","author":"Klein","year":"2020","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"7692","key":"10.1016\/j.bbr.2020.112532_bib0350","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1038\/nature25509","article-title":"Ketamine blocks bursting in the lateral habenula to rapidly relieve depression","volume":"554","author":"Yang","year":"2018","journal-title":"Nature"},{"issue":"2","key":"10.1016\/j.bbr.2020.112532_bib0355","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1002\/neu.20025","article-title":"Chronic stress alters dendritic morphology in rat medial prefrontal cortex","volume":"60","author":"Cook","year":"2004","journal-title":"J. Neurobiol."},{"issue":"13","key":"10.1016\/j.bbr.2020.112532_bib0360","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.jpsychires.2010.01.006","article-title":"Interaction of childhood stress with hippocampus and prefrontal cortex volume reduction in major depression","volume":"44","author":"Frodl","year":"2010","journal-title":"J. Psychiatr. Res."},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0365","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.neuroscience.2009.04.057","article-title":"Chronic stress effects on dendritic morphology in medial prefrontal cortex: sex differences and estrogen dependence","volume":"162","author":"Garrett","year":"2009","journal-title":"Neuroscience"},{"key":"10.1016\/j.bbr.2020.112532_bib0370","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1146\/annurev.neuro.27.070203.144130","article-title":"The medial temporal lobe","volume":"27","author":"Squire","year":"2004","journal-title":"Annu. Rev. Neurosci."},{"issue":"11","key":"10.1016\/j.bbr.2020.112532_bib0375","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1176\/appi.ajp.161.11.1957","article-title":"Hippocampal volume and depression: a meta-analysis of MRI studies","volume":"161","author":"Videbech","year":"2004","journal-title":"Am. J. Psychiatry"},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0380","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.biopsych.2017.11.028","article-title":"Calcium\/Calmodulin-dependent protein kinase II and eukaryotic elongation factor 2 kinase pathways mediate the antidepressant action of ketamine","volume":"84","author":"Adaikkan","year":"2018","journal-title":"Biol. Psychiatry"},{"issue":"5994","key":"10.1016\/j.bbr.2020.112532_bib0385","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1126\/science.1190287","article-title":"mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists","volume":"329","author":"Li","year":"2010","journal-title":"Science"},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0390","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.biopsych.2017.05.016","article-title":"Mechanistic target of rapamycin-independent antidepressant effects of (R)-Ketamine in a social defeat stress model","volume":"83","author":"Yang","year":"2018","journal-title":"Biol. Psychiatry"},{"issue":"6","key":"10.1016\/j.bbr.2020.112532_bib0395","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.biopsych.2015.12.025","article-title":"Sex differences in effects of ketamine on behavior, spine density, and synaptic proteins in socially isolated rats","volume":"80","author":"Sarkar","year":"2016","journal-title":"Biol. Psychiatry"},{"issue":"4","key":"10.1016\/j.bbr.2020.112532_bib0400","doi-asserted-by":"crossref","first-page":"2134","DOI":"10.1152\/jn.00069.2006","article-title":"Ventral hippocampal neurons project axons simultaneously to the medial prefrontal cortex and amygdala in the rat","volume":"96","author":"Ishikawa","year":"2006","journal-title":"J. Neurophysiol."},{"issue":"4","key":"10.1016\/j.bbr.2020.112532_bib0405","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/cne.903130404","article-title":"Distribution of hippocampal CA1 and subicular efferents in the prefrontal cortex of the rat studied by means of anterograde transport of Phaseolus vulgaris-leucoagglutinin","volume":"313","author":"Jay","year":"1991","journal-title":"J. Comp. Neurol."},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0410","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0306-4522(03)00150-7","article-title":"Individual nucleus accumbens-projection neurons receive both basolateral amygdala and ventral subicular afferents in rats","volume":"119","author":"French","year":"2003","journal-title":"Neuroscience"},{"issue":"4","key":"10.1016\/j.bbr.2020.112532_bib0415","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/cne.10336","article-title":"Comparison of hippocampal, amygdala, and perirhinal projections to the nucleus accumbens: combined anterograde and retrograde tracing study in the Macaque brain","volume":"450","author":"Friedman","year":"2002","journal-title":"J. Comp. Neurol."},{"issue":"2","key":"10.1016\/j.bbr.2020.112532_bib0420","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1016\/j.neuroscience.2009.10.036","article-title":"Pathways from the ventral hippocampus and caudal amygdala to forebrain regions that regulate sensorimotor gating in the rat","volume":"165","author":"Miller","year":"2010","journal-title":"Neuroscience"},{"issue":"2","key":"10.1016\/j.bbr.2020.112532_bib0425","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/0006-8993(77)90880-0","article-title":"Efferent connections of the hippocampal formation in the rat","volume":"124","author":"Meibach","year":"1977","journal-title":"Brain Res."},{"issue":"9","key":"10.1016\/j.bbr.2020.112532_bib0430","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/j.tips.2011.05.001","article-title":"Hippocampal dysregulation of dopamine system function and the pathophysiology of schizophrenia","volume":"32","author":"Lodge","year":"2011","journal-title":"Trends Pharmacol. Sci."},{"issue":"9","key":"10.1016\/j.bbr.2020.112532_bib0435","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1016\/S0006-3223(99)00177-8","article-title":"Neural plasticity to stress and antidepressant treatment","volume":"46","author":"Duman","year":"1999","journal-title":"Biol. Psychiatry"},{"issue":"4","key":"10.1016\/j.bbr.2020.112532_bib0440","first-page":"354","article-title":"Hippocampal perineuronal nets are required for the sustained antidepressant effect of ketamine","volume":"20","author":"Donegan","year":"2017","journal-title":"Int. J. Neuropsychopharmacol."},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0445","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/0006-8993(81)90192-X","article-title":"A direct projection from Ammon\u2019s horn to prefrontal cortex in the rat","volume":"217","author":"Swanson","year":"1981","journal-title":"Brain Res."},{"issue":"17","key":"10.1016\/j.bbr.2020.112532_bib0450","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1007\/s00213-015-3957-3","article-title":"Antidepressant-like cognitive and behavioral effects of acute ketamine administration associated with plasticity in the ventral hippocampus to medial prefrontal cortex pathway","volume":"232","author":"Jett","year":"2015","journal-title":"Psychopharmacology"},{"issue":"12","key":"10.1016\/j.bbr.2020.112532_bib0455","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.biopsych.2014.04.014","article-title":"Restoring mood balance in depression: ketamine reverses deficit in dopamine-dependent synaptic plasticity","volume":"76","author":"Belujon","year":"2014","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.bbr.2020.112532_bib0460","doi-asserted-by":"crossref","DOI":"10.1038\/s41380-019-0400-x","article-title":"Neurobiology of rapid-acting antidepressants: convergent effects on GluA1-synaptic function","author":"Duman","year":"2019","journal-title":"Mol. Psychiatry"},{"issue":"5","key":"10.1016\/j.bbr.2020.112532_bib0465","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1016\/j.neuron.2019.02.005","article-title":"Ketamine: a paradigm shift for depression research and treatment","volume":"101","author":"Krystal","year":"2019","journal-title":"Neuron"},{"key":"10.1016\/j.bbr.2020.112532_bib0470","doi-asserted-by":"crossref","DOI":"10.1016\/j.pnpbp.2019.109668","article-title":"The role of NMDA receptor in neurobiology and treatment of major depressive disorder: evidence from translational research","volume":"94","author":"Amidfar","year":"2019","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"issue":"2","key":"10.1016\/j.bbr.2020.112532_bib0475","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1093\/ijnp\/pyy094","article-title":"Glutamatergic neurotransmission: pathway to developing novel rapid-acting antidepressant treatments","volume":"22","author":"Kadriu","year":"2019","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"10.1016\/j.bbr.2020.112532_bib0480","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jad.2014.02.017","article-title":"Do the dissociative side effects of ketamine mediate its antidepressant effects?","volume":"159","author":"Luckenbaugh","year":"2014","journal-title":"J. Affect. Disord."},{"key":"10.1016\/j.bbr.2020.112532_bib0485","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1016\/j.jad.2018.02.049","article-title":"Features of dissociation differentially predict antidepressant response to ketamine in treatment-resistant depression","volume":"232","author":"Niciu","year":"2018","journal-title":"J. Affect. Disord."},{"issue":"4","key":"10.1016\/j.bbr.2020.112532_bib0490","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1016\/S0306-4522(00)00442-5","article-title":"GABA(A) receptors: immunocytochemical distribution of 13 subunits in the adult rat brain","volume":"101","author":"Pirker","year":"2000","journal-title":"Neuroscience"},{"issue":"5","key":"10.1016\/j.bbr.2020.112532_bib0495","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1124\/mol.54.5.928","article-title":"Rat and human hippocampal alpha5 subunit-containing gamma-aminobutyric AcidA receptors have alpha5 beta3 gamma2 pharmacological characteristics","volume":"54","author":"Sur","year":"1998","journal-title":"Mol. Pharmacol."},{"issue":"3","key":"10.1016\/j.bbr.2020.112532_bib0500","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1523\/JNEUROSCI.12-03-01040.1992","article-title":"The distribution of 13 GABAA receptor subunit mRNAs in the rat brain. I. Telencephalon, diencephalon, mesencephalon","volume":"12","author":"Wisden","year":"1992","journal-title":"J. Neurosci."},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0505","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/cne.10102","article-title":"Intact sorting, targeting, and clustering of gamma-aminobutyric acid A receptor subtypes in hippocampal neurons in vitro","volume":"443","author":"Brunig","year":"2002","journal-title":"J. Comp. Neurol."},{"issue":"3","key":"10.1016\/j.bbr.2020.112532_bib0510","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1523\/JNEUROSCI.22-03-00684.2002","article-title":"GABAergic innervation organizes synaptic and extrasynaptic GABAA receptor clustering in cultured hippocampal neurons","volume":"22","author":"Christie","year":"2002","journal-title":"J. Neurosci."},{"issue":"13","key":"10.1016\/j.bbr.2020.112532_bib0515","doi-asserted-by":"crossref","first-page":"8980","DOI":"10.1073\/pnas.142288699","article-title":"Trace fear conditioning involves hippocampal alpha5 GABA(A) receptors","volume":"99","author":"Crestani","year":"2002","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"2-3","key":"10.1016\/j.bbr.2020.112532_bib0520","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0304-3940(98)00397-8","article-title":"Independent assembly and subcellular targeting of GABA(A)-receptor subtypes demonstrated in mouse hippocampal and olfactory neurons in vivo","volume":"249","author":"Fritschy","year":"1998","journal-title":"Neurosci. Lett."},{"issue":"10","key":"10.1016\/j.bbr.2020.112532_bib0525","doi-asserted-by":"crossref","first-page":"3662","DOI":"10.1073\/pnas.0307231101","article-title":"Tonic inhibition in mouse hippocampal CA1 pyramidal neurons is mediated by alpha5 subunit-containing gamma-aminobutyric acid type A receptors","volume":"101","author":"Caraiscos","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"issue":"5","key":"10.1016\/j.bbr.2020.112532_bib0530","doi-asserted-by":"crossref","first-page":"2796","DOI":"10.1152\/jn.01122.2005","article-title":"Hippocampal network hyperactivity after selective reduction of tonic inhibition in GABA A receptor alpha5 subunit-deficient mice","volume":"95","author":"Glykys","year":"2006","journal-title":"J. Neurophysiol."},{"issue":"3","key":"10.1016\/j.bbr.2020.112532_bib0535","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1002\/cne.21115","article-title":"Synaptic and nonsynaptic localization of GABAA receptors containing the alpha5 subunit in the rat brain","volume":"499","author":"Serwanski","year":"2006","journal-title":"J. Comp. Neurol."},{"issue":"1-2","key":"10.1016\/j.bbr.2020.112532_bib0540","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0006-8993(99)01152-X","article-title":"Autoradiographic localization of alpha5 subunit-containing GABAA receptors in rat brain","volume":"822","author":"Sur","year":"1999","journal-title":"Brain Res."},{"issue":"2","key":"10.1016\/j.bbr.2020.112532_bib0545","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/S0169-328X(00)00133-9","article-title":"Expression of GABA(A) receptor alpha5 subunit-like immunoreactivity in human hippocampus","volume":"80","author":"Wainwright","year":"2000","journal-title":"Brain Res. Mol. Brain Res."},{"issue":"6","key":"10.1016\/j.bbr.2020.112532_bib0550","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1093\/cercor\/bhm160","article-title":"Synaptic alpha 5 subunit-containing GABAA receptors mediate IPSPs elicited by dendrite-preferring cells in rat neocortex","volume":"18","author":"Ali","year":"2008","journal-title":"Cereb. Cortex"},{"issue":"Pt 20","key":"10.1016\/j.bbr.2020.112532_bib0555","doi-asserted-by":"crossref","first-page":"4885","DOI":"10.1113\/jphysiol.2011.215244","article-title":"Age-dependent remodelling of inhibitory synapses onto hippocampal CA1 oriens-lacunosum moleculare interneurons","volume":"589","author":"Salesse","year":"2011","journal-title":"J. Physiol."},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0560","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1038\/s41467-018-06004-8","article-title":"Dendrite-targeting interneurons control synaptic NMDA-receptor activation via nonlinear alpha5-GABAA receptors","volume":"9","author":"Schulz","year":"2018","journal-title":"Nat. Commun."},{"issue":"3","key":"10.1016\/j.bbr.2020.112532_bib0565","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1152\/jn.91203.2008","article-title":"GABAA receptor alpha5 subunits contribute to GABAA,slow synaptic inhibition in mouse hippocampus","volume":"101","author":"Zarnowska","year":"2009","journal-title":"J. Neurophysiol."},{"issue":"5","key":"10.1016\/j.bbr.2020.112532_bib0570","doi-asserted-by":"crossref","first-page":"788","DOI":"10.1523\/JNEUROSCI.0567-18.2018","article-title":"Input-specific synaptic location and function of the alpha5 GABAA receptor subunit in the mouse CA1 hippocampal neurons","volume":"39","author":"Magnin","year":"2019","journal-title":"J. Neurosci."},{"issue":"9-10","key":"10.1016\/j.bbr.2020.112532_bib0575","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1016\/S0028-3908(96)00061-5","article-title":"[3H]L-655,708, a novel ligand selective for the benzodiazepine site of GABAA receptors which contain the alpha 5 subunit","volume":"35","author":"Quirk","year":"1996","journal-title":"Neuropharmacology"},{"issue":"6","key":"10.1016\/j.bbr.2020.112532_bib0580","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1093\/ijnp\/pyx003","article-title":"Selective pharmacological augmentation of hippocampal activity produces a sustained antidepressant-like response without abuse-related or psychotomimetic effects","volume":"20","author":"Carreno","year":"2017","journal-title":"Int. J. Neuropsychopharmacol."},{"issue":"11","key":"10.1016\/j.bbr.2020.112532_bib0585","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.1038\/npp.2015.112","article-title":"Rapid antidepressant action and restoration of excitatory synaptic strength after chronic stress by negative modulators of Alpha5-Containing GABAA receptors","volume":"40","author":"Fischell","year":"2015","journal-title":"Neuropsychopharmacology"},{"issue":"1","key":"10.1016\/j.bbr.2020.112532_bib0590","doi-asserted-by":"crossref","DOI":"10.1523\/ENEURO.0285-16.2017","article-title":"A negative allosteric modulator for alpha5 subunit-containing GABA receptors exerts a rapid and persistent antidepressant-like action without the side effects of the NMDA receptor antagonist ketamine in mice","volume":"4","author":"Zanos","year":"2017","journal-title":"eNeuro"},{"issue":"5","key":"10.1016\/j.bbr.2020.112532_bib0595","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1021\/acschemneuro.9b00148","article-title":"Insight into novel treatment for cognitive dysfunctions across disorders","volume":"10","author":"Prevot","year":"2019","journal-title":"ACS Chem. Neurosci."},{"issue":"2","key":"10.1016\/j.bbr.2020.112532_bib0600","first-page":"84","article-title":"Novel benzodiazepine-like ligands with various anxiolytic, antidepressant, or pro-cognitive profiles","volume":"5","author":"Prevot","year":"2019","journal-title":"Mol. Neuropsychiatry"}],"container-title":["Behavioural Brain Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0166432819315980?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0166432819315980?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T13:18:22Z","timestamp":1759065502000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0166432819315980"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4]]},"references-count":120,"alternative-id":["S0166432819315980"],"URL":"https:\/\/doi.org\/10.1016\/j.bbr.2020.112532","relation":{},"ISSN":["0166-4328"],"issn-type":[{"value":"0166-4328","type":"print"}],"subject":[],"published":{"date-parts":[[2020,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Ketamine: Leading us into the future for development of antidepressants","name":"articletitle","label":"Article Title"},{"value":"Behavioural Brain Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bbr.2020.112532","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"112532"}}