{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T04:01:28Z","timestamp":1789790488803,"version":"4.0.1"},"reference-count":58,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2016,1,4]],"date-time":"2016-01-04T00:00:00Z","timestamp":1451865600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2016,1,4]],"date-time":"2016-01-04T00:00:00Z","timestamp":1451865600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["08-M-0196"],"award-info":[{"award-number":["08-M-0196"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000874","name":"Brain and Behavior Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000874","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009670","name":"NARSAD","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009670","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Psychopharmacology"],"published-print":{"date-parts":[[2016,3]]},"DOI":"10.1007\/s00213-015-4195-4","type":"journal-article","created":{"date-parts":[[2016,1,4]],"date-time":"2016-01-04T05:00:02Z","timestamp":1451883602000},"page":"1119-1130","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":73,"title":["A randomized, placebo-controlled pilot trial of the delta opioid receptor agonist AZD2327 in anxious depression"],"prefix":"10.1007","volume":"233","author":[{"given":"Erica M.","family":"Richards","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel C.","family":"Mathews","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Luckenbaugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn F.","family":"Ionescu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Machado-Vieira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark J.","family":"Niciu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wallace C.","family":"Duncan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neal M.","family":"Nolan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose A.","family":"Franco-Chaves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hudzik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Maciag","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Cross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark A.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Carlos A.","family":"Zarate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,1,4]]},"reference":[{"key":"4195_CR1","unstructured":"Alkermes PLC (2015) Alkermes announces positive results from study of ALKS 5461 for treatment of major depressive disorder"},{"key":"4195_CR2","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1192\/bjp.bp.106.027169","volume":"190","author":"C Andreescu","year":"2007","unstructured":"Andreescu C, Lenze EJ, Dew MA, Begley AE, Mulsant BH, Dombrovski AY, Pollock BG, Stack J, Miller MD, Reynolds CF (2007) Effect of comorbid anxiety on treatment response and relapse risk in late-life depression: controlled study. Br J Psychiatry 190:344\u2013349","journal-title":"Br J Psychiatry"},{"key":"4195_CR3","first-page":"203","volume":"53","author":"AK Baker","year":"2002","unstructured":"Baker AK, Hoffman VL, Meert TF (2002) Interactions of NMDA antagonists and an alpha 2 agonist with mu, delta and kappa opioids in an acute nociception assay. Acta Anaesthesiol Belg 53:203\u2013212","journal-title":"Acta Anaesthesiol Belg"},{"key":"4195_CR4","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/0306-4522(88)90283-7","volume":"27","author":"TP Blackburn","year":"1988","unstructured":"Blackburn TP, Cross AJ, Hille C, Slater P (1988) Autoradiographic localization of delta opiate receptors in rat and human brain. Neuroscience 27:497\u2013506","journal-title":"Neuroscience"},{"key":"4195_CR5","doi-asserted-by":"publisher","first-page":"763","DOI":"10.3109\/15622971003611319","volume":"11","author":"L Bocchio-Chiavetto","year":"2010","unstructured":"Bocchio-Chiavetto L, Bagnardi V, Zanardini R, Molteni R, Nielsen MG, Placentino A, Giovannini C, Rillosi L, Ventriglia M, Riva MA, Gennarelli M (2010) Serum and plasma BDNF levels in major depression: a replication study and meta-analyses. World J Biol Psychiatry 11:763\u2013773","journal-title":"World J Biol Psychiatry"},{"key":"4195_CR6","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/j.neuropharm.2013.08.027","volume":"77","author":"KE Bosse","year":"2014","unstructured":"Bosse KE, Jutkiewicz EM, Schultz-Kuszak KN, Mabrouk OS, Kennedy RT, Gnegy ME, Traynor JR (2014) Synergistic activity between the delta-opioid agonist SNC80 and amphetamine occurs via a glutamatergic NMDA-receptor dependent mechanism. Neuropharmacology 77:19\u201327","journal-title":"Neuropharmacology"},{"key":"4195_CR7","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1016\/S0893-133X(01)00413-4","volume":"26","author":"DC Broom","year":"2002","unstructured":"Broom DC, Jutkiewicz EM, Folk JE, Traynor JR, Rice KC, Woods JH (2002) Nonpeptidic delta-opioid receptor agonists reduce immobility in the forced swim assay in rats. Neuropsychopharmacology 26:744\u2013755","journal-title":"Neuropsychopharmacology"},{"key":"4195_CR8","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1002\/cne.1370","volume":"440","author":"CM Cahill","year":"2001","unstructured":"Cahill CM, McClellan KA, Morinville A, Hoffert C, Hubatsch D, O\u2019Donnell D, Beaudet A (2001) Immunohistochemical distribution of delta opioid receptors in the rat central nervous system: evidence for somatodendritic labeling and antigen-specific cellular compartmentalization. J Comp Neurol 440:65\u201384","journal-title":"J Comp Neurol"},{"key":"4195_CR9","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1124\/mol.51.4.583","volume":"51","author":"YC Cai","year":"1997","unstructured":"Cai YC, Ma L, Fan GH, Zhao J, Jiang LZ, Pei G (1997) Activation of N-methyl-D-aspartate receptor attenuates acute responsiveness of delta-opioid receptors. Mol Pharmacol 51:583\u2013587","journal-title":"Mol Pharmacol"},{"key":"4195_CR10","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1016\/j.jpsychires.2013.04.008","volume":"47","author":"A Clark-Raymond","year":"2013","unstructured":"Clark-Raymond A, Halaris A (2013) VEGF and depression: a comprehensive assessment of clinical data. J Psychiatr Res 47:1080\u20131087","journal-title":"J Psychiatr Res"},{"key":"4195_CR11","first-page":"115","volume":"1","author":"P Cleary","year":"1977","unstructured":"Cleary P, Guy W (1977) Factor analysis of the Hamilton depression scale. Drugs Exp Clin Res 1:115\u2013120","journal-title":"Drugs Exp Clin Res"},{"key":"4195_CR12","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1016\/j.biopsych.2012.03.029","volume":"72","author":"BR Cornwell","year":"2012","unstructured":"Cornwell BR, Salvadore G, Furey M, Marquardt CA, Brutsche NE, Grillon C, Zarate CAJ (2012) Synaptic potentiation is critical for rapid antidepressant response to ketamine in treatment-resistant major depression. Biol Psychiatry 72:555\u2013561","journal-title":"Biol Psychiatry"},{"key":"4195_CR13","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/S0006-8993(98)01256-6","volume":"817","author":"JM de Gandarias","year":"1999","unstructured":"de Gandarias JM, Echevarria E, Acebes I, Abecia LC, Casis O, Casis L (1999) Effects of fluoxetine administration on mu-opoid receptor immunostaining in the rat forebrain. Brain Res 817:236\u2013240","journal-title":"Brain Res"},{"key":"4195_CR14","doi-asserted-by":"publisher","first-page":"621","DOI":"10.1177\/0269881108097723","volume":"24","author":"K Domschke","year":"2010","unstructured":"Domschke K, Deckert J, Arolt V, Baune BT (2010) Anxious versus non-anxious depression: difference in treatment outcome. J Psychopharmacol 24:621\u2013622","journal-title":"J Psychopharmacol"},{"key":"4195_CR15","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1385\/NMM:5:1:011","volume":"5","author":"RS Duman","year":"2004","unstructured":"Duman RS (2004) Role of neurotrophic factors in the etiology and treatment of mood disorders. Neuromol Med 5:11\u201325","journal-title":"Neuromol Med"},{"key":"4195_CR16","doi-asserted-by":"publisher","first-page":"1409","DOI":"10.1017\/S1461145714000273","volume":"17","author":"B Elfving","year":"2014","unstructured":"Elfving B, Buttenschon HN, Foldager L, Poulsen PH, Grynderup MB, Hansen AM, Kolstad HA, Kaerlev L, Mikkelsen S, Borglum AD, Wegener G, Mors O (2014) Depression and BMI influences the serum vascular endothelial growth factor level. Int J Neuropsychopharmacol 17:1409\u20131417","journal-title":"Int J Neuropsychopharmacol"},{"key":"4195_CR17","doi-asserted-by":"publisher","first-page":"1512","DOI":"10.1038\/sj.npp.1300459","volume":"29","author":"PV Escriba","year":"2004","unstructured":"Escriba PV, Ozaita A, Garcia-Sevilla JA (2004) Increased mRNA expression of alpha2A-adrenoceptors, serotonin receptors and mu-opioid receptors in the brains of suicide victims. Neuropsychopharmacology 29:1512\u20131521","journal-title":"Neuropsychopharmacology"},{"key":"4195_CR18","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/j.jad.2012.04.029","volume":"142","author":"A Farabaugh","year":"2012","unstructured":"Farabaugh A, Alpert J, Wisniewski SR, Otto MW, Fava M, Baer L, Perlis R, Friedman E, Nyer M, Bitran S, Balasubramani GK, Inamori A, Trivedi M, Thase ME (2012) Cognitive therapy for anxious depression in STAR(*) D: what have we learned? J Affect Disord 142:213\u2013218","journal-title":"J Affect Disord"},{"key":"4195_CR19","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/S0010-440X(00)90140-8","volume":"41","author":"M Fava","year":"2000","unstructured":"Fava M, Rankin MA, Wright EC, Alpert JE, Nierenberg AA, Pava J, Rosenbaum JF (2000) Anxiety disorders in major depression. Compr Psychiatry 41:97\u2013102","journal-title":"Compr Psychiatry"},{"key":"4195_CR20","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1176\/appi.ajp.2007.06111868","volume":"165","author":"M Fava","year":"2008","unstructured":"Fava M, Rush AJ, Alpert JE, Balasubramani GK, Wisniewski SR, Carmin CN, Biggs MM, Zisook S, Leuchter A, Howland R, Warden D, Trivedi MH (2008) Difference in treatment outcome in outpatients with anxious versus nonanxious depression: a STAR*D report. Am J Psychiatry 165:342\u2013351","journal-title":"Am J Psychiatry"},{"key":"4195_CR21","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1038\/76061","volume":"25","author":"D Filliol","year":"2000","unstructured":"Filliol D, Ghozland S, Chluba J, Martin M, Matthes HW, Simonin F, Befort K, Gaveriaux-Ruff C, Dierich A, LeMeur M, Valverde O, Maldonado R, Kieffer BL (2000) Mice deficient for delta- and mu-opioid receptors exhibit opposing alterations of emotional responses. Nat Genet 25:195\u2013200","journal-title":"Nat Genet"},{"key":"4195_CR22","volume-title":"Structured Clinical Interview for DSM-IV TR Axis I Disorders, Research Version, Patient Edition (SCID-I\/P)","author":"MB First","year":"2001","unstructured":"First MB, Spitzer RL, Gibbon M, Williams AR (2001) Structured Clinical Interview for DSM-IV TR Axis I Disorders, Research Version, Patient Edition (SCID-I\/P). New York State Psychiatric Institute, Biometrics Research, New York"},{"key":"4195_CR23","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1016\/j.jad.2013.06.055","volume":"151","author":"M Fornaro","year":"2013","unstructured":"Fornaro M, Rocchi G, Escelsior A, Contini P, Ghio M, Colicchio S, De Berardis D, Amore M, Fornaro P, Martino M (2013) VEGF plasma level variations in duloxetine-treated patients with major depression. J Affect Disord 151:590\u2013595","journal-title":"J Affect Disord"},{"key":"4195_CR24","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1016\/j.neuroscience.2004.10.016","volume":"130","author":"K Fusa","year":"2005","unstructured":"Fusa K, Takahashi I, Watanabe S, Aono Y, Ikeda H, Saigusa T, Nagase H, Suzuki T, Koshikawa N, Cools AR (2005) The non-peptidic delta opioid receptor agonist TAN-67 enhances dopamine efflux in the nucleus accumbens of freely moving rats via a mechanism that involves both glutamate and free radicals. Neuroscience 130:745\u2013755","journal-title":"Neuroscience"},{"key":"4195_CR25","doi-asserted-by":"publisher","first-page":"6239","DOI":"10.1073\/pnas.77.10.6239","volume":"77","author":"RR Goodman","year":"1980","unstructured":"Goodman RR, Snyder SH, Kuhar MJ, Young WS 3rd (1980) Differentiation of delta and mu opiate receptor localizations by light microscopic autoradiography. Proc Natl Acad Sci U S A 77:6239\u20136243","journal-title":"Proc Natl Acad Sci U S A"},{"key":"4195_CR26","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1002\/da.20672","volume":"27","author":"A Greenlee","year":"2010","unstructured":"Greenlee A, Karp JF, Dew MA, Houck P, Andreescu C, Reynolds CF 3rd (2010) Anxiety impairs depression remission in partial responders during extended treatment in late-life. Depress Anxiety 27:451\u2013456","journal-title":"Depress Anxiety"},{"key":"4195_CR27","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1016\/0006-8993(90)91301-V","volume":"530","author":"R Gross-Isseroff","year":"1990","unstructured":"Gross-Isseroff R, Dillon KA, Israeli M, Biegon A (1990) Regionally selective increases in mu opioid receptor density in the brains of suicide victims. Brain Res 530:312\u2013316","journal-title":"Brain Res"},{"key":"4195_CR28","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1016\/j.clinph.2005.07.007","volume":"116","author":"CS Herrmann","year":"2005","unstructured":"Herrmann CS, Demiralp T (2005) Human EEG gamma oscillations in neuropsychiatric disorders. Clin Neurophysiol 116:2719\u20132733","journal-title":"Clin Neurophysiol"},{"key":"4195_CR29","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1124\/jpet.111.179432","volume":"338","author":"TJ Hudzik","year":"2011","unstructured":"Hudzik TJ, Maciag C, Smith MA, Caccese R, Pietras MR, Bui KH, Coupal M, Adam L, Payza K, Griffin A, Smagin G, Song D, Swedberg MD, Brown W (2011) Preclinical pharmacology of AZD2327: a highly selective agonist of the delta-opioid receptor. J Pharmacol Exp Ther 338:195\u2013204","journal-title":"J Pharmacol Exp Ther"},{"key":"4195_CR30","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.pbb.2014.05.009","volume":"124","author":"TJ Hudzik","year":"2014","unstructured":"Hudzik TJ, Pietras MR, Caccese R, Bui KH, Yocca F, Paronis CA, Swedberg MD (2014) Effects of the delta opioid agonist AZD2327 upon operant behaviors and assessment of its potential for abuse. Pharmacol Biochem Behav 124:48\u201357","journal-title":"Pharmacol Biochem Behav"},{"key":"4195_CR31","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1016\/j.pnpbp.2006.12.011","volume":"31","author":"J Iga","year":"2007","unstructured":"Iga J, Ueno S, Yamauchi K, Numata S, Tayoshi-Shibuya S, Kinouchi S, Nakataki M, Song H, Hokoishi K, Tanabe H, Sano A, Ohmori T (2007) Gene expression and association analysis of vascular endothelial growth factor in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 31:658\u2013663","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"key":"4195_CR32","doi-asserted-by":"crossref","unstructured":"Ionescu DF, Niciu MJ, Henter ID, Zarate CA (2013) Defining anxious depression: a review of the literature. CNS Spectr 1\u20139","DOI":"10.1017\/S1092852913000114"},{"key":"4195_CR33","doi-asserted-by":"crossref","unstructured":"Ionescu DF, Niciu MJ, Richards EM, Zarate CA, Jr. (2014) Pharmacologic treatment of dimensional anxious depression: a review. Prim Care Companion CNS Disord 16","DOI":"10.4088\/PCC.13r01621"},{"key":"4195_CR34","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1124\/mi.6.3.7","volume":"6","author":"EM Jutkiewicz","year":"2006","unstructured":"Jutkiewicz EM (2006) The antidepressant-like effects of delta-opioid receptor agonists. Mol Interv 6:162\u2013169","journal-title":"Mol Interv"},{"key":"4195_CR35","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.psyneuen.2008.09.016","volume":"34","author":"KG Kahl","year":"2009","unstructured":"Kahl KG, Bens S, Ziegler K, Rudolf S, Kordon A, Dibbelt L, Schweiger U (2009) Angiogenic factors in patients with current major depressive disorder comorbid with borderline personality disorder. Psychoneuroendocrinology 34:353\u2013357","journal-title":"Psychoneuroendocrinology"},{"key":"4195_CR36","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1001\/archpsyc.63.11.1199","volume":"63","author":"SE Kennedy","year":"2006","unstructured":"Kennedy SE, Koeppe RA, Young EA, Zubieta JK (2006) Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women. Arch Gen Psychiatry 63:1199\u20131208","journal-title":"Arch Gen Psychiatry"},{"key":"4195_CR37","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1016\/j.biopsych.2011.03.017","volume":"70","author":"AT Knoll","year":"2011","unstructured":"Knoll AT, Muschamp JW, Sillivan SE, Ferguson D, Dietz DM, Meloni EG, Carroll FI, Nestler EJ, Konradi C, Carlezon WA Jr (2011) Kappa opioid receptor signaling in the basolateral amygdala regulates conditioned fear and anxiety in rats. Biol Psychiatry 70:425\u2013433","journal-title":"Biol Psychiatry"},{"key":"4195_CR38","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/j.jad.2011.07.021","volume":"136","author":"BH Lee","year":"2012","unstructured":"Lee BH, Kim YK (2012) Increased plasma VEGF levels in major depressive or manic episodes in patients with mood disorders. J Affect Disord 136:181\u2013184","journal-title":"J Affect Disord"},{"key":"4195_CR39","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0031-6997(24)01340-1","volume":"49","author":"JH Lin","year":"1997","unstructured":"Lin JH, Lu AY (1997) Role of pharmacokinetics and metabolism in drug discovery and development. Pharmacol Rev 49:403\u2013449","journal-title":"Pharmacol Rev"},{"key":"4195_CR40","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1016\/j.tins.2012.11.002","volume":"36","author":"PE Lutz","year":"2013","unstructured":"Lutz PE, Kieffer BL (2013) Opioid receptors: distinct roles in mood disorders. Trends Neurosci 36:195\u2013206","journal-title":"Trends Neurosci"},{"key":"4195_CR41","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/0891-0618(93)90010-2","volume":"6","author":"A Mansour","year":"1993","unstructured":"Mansour A, Thompson RC, Akil H, Watson SJ (1993) Delta opioid receptor mRNA distribution in the brain: comparison to delta receptor binding and proenkephalin mRNA. J Chem Neuroanat 6:351\u2013362","journal-title":"J Chem Neuroanat"},{"key":"4195_CR42","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.ejphar.2007.03.031","volume":"566","author":"PS Naidu","year":"2007","unstructured":"Naidu PS, Lichtman AH, Archer CC, May EL, Harris LS, Aceto MD (2007) NIH 11082 produces anti-depressant-like activity in the mouse tail-suspension test through a delta-opioid receptor mechanism of action. Eur J Pharmacol 566:132\u2013136","journal-title":"Eur J Pharmacol"},{"key":"4195_CR43","volume-title":"Depression: management of depression in primary and secondary care. Clinical Guideline 23","author":"National Institute for Clinical Excellence (NICE)","year":"2004","unstructured":"National Institute for Clinical Excellence (NICE) (2004) Depression: management of depression in primary and secondary care. Clinical Guideline 23. NICE, London"},{"key":"4195_CR44","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/s00213-004-1894-7","volume":"176","author":"A Ortega-Alvaro","year":"2004","unstructured":"Ortega-Alvaro A, Acebes A, Saracibar G, Echevarria E, Casis L, Mico JA (2004) Effect of the antidepressant nefazodone on the density of cells expressing mu-opioid receptors in discrete brain areas processing sensory and affective dimensions of pain. Psychopharmacology Berl 176:305\u2013311","journal-title":"Psychopharmacology Berl"},{"key":"4195_CR45","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S0022-3565(25)21481-1","volume":"230","author":"F Porreca","year":"1984","unstructured":"Porreca F, Mosberg HI, Hurst R, Hruby VJ, Burks TF (1984) Roles of mu, delta and kappa opioid receptors in spinal and supraspinal mediation of gastrointestinal transit effects and hot-plate analgesia in the mouse. J Pharmacol Exp Ther 230:341\u2013348","journal-title":"J Pharmacol Exp Ther"},{"issue":"Suppl 1","key":"4195_CR46","doi-asserted-by":"publisher","first-page":"227","DOI":"10.1016\/0024-3205(83)90484-8","volume":"33","author":"R Quirion","year":"1983","unstructured":"Quirion R, Zajac JM, Morgat JL, Roques BP (1983) Autoradiographic distribution of mu and delta opiate receptors in rat brain using highly selective ligands. Life Sci 33(Suppl 1):227\u2013230","journal-title":"Life Sci"},{"key":"4195_CR47","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1159\/000112867","volume":"81","author":"JD Reindl","year":"2008","unstructured":"Reindl JD, Rowan K, Carey AN, Peng X, Neumeyer JL, McLaughlin JP (2008) Antidepressant-like effects of the novel kappa opioid antagonist MCL-144B in the forced-swim test. Pharmacology 81:229\u2013235","journal-title":"Pharmacology"},{"key":"4195_CR48","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1017\/S0033291711002170","volume":"42","author":"AJ Rush","year":"2012","unstructured":"Rush AJ, Wisniewski SR, Zisook S, Fava M, Sung SC, Haley CL, Chan HN, Gilmer WS, Warden D, Nierenberg AA, Balasubramani GK, Gaynes BN, Trivedi MH, Hollon SD (2012) Is prior course of illness relevant to acute or longer-term outcomes in depressed out-patients? A STAR*D report. Psychol Med 42:1131\u20131149","journal-title":"Psychol Med"},{"key":"4195_CR49","doi-asserted-by":"publisher","first-page":"374","DOI":"10.1254\/jphs.FPJ04014X","volume":"95","author":"A Saitoh","year":"2004","unstructured":"Saitoh A, Kimura Y, Suzuki T, Kawai K, Nagase H, Kamei J (2004) Potential anxiolytic and antidepressant-like activities of SNC80, a selective delta-opioid agonist, in behavioral models in rodents. J Pharmacol Sci 95:374\u2013380","journal-title":"J Pharmacol Sci"},{"key":"4195_CR50","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1176\/ajp.147.8.1025","volume":"147","author":"WC Sanderson","year":"1990","unstructured":"Sanderson WC, Beck AT, Beck J (1990) Syndrome comorbidity in patients with major depression or dysthymia: prevalence and temporal relationships. Am J Psychiatry 147:1025\u20131028","journal-title":"Am J Psychiatry"},{"key":"4195_CR51","doi-asserted-by":"publisher","first-page":"S496","DOI":"10.1016\/S0924-977X(08)70743-0","volume":"18","author":"GN Smagin","year":"2008","unstructured":"Smagin GN, Song D, Medd A, Cross AJ, Hudzik T, Mrzljak L (2008) Neurochemical validation of centrally active delta-opioid receptor agonists as novel treatment of anxiety disorders. Eur Neuropsychopharmacol 18:S496","journal-title":"Eur Neuropsychopharmacol"},{"key":"4195_CR52","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.janxdis.2012.02.010","volume":"26","author":"S Taylor","year":"2012","unstructured":"Taylor S, Abramowitz JS, McKay D (2012) Non-adherence and non-response in the treatment of anxiety disorders. J Anxiety Disord 26:583\u2013589","journal-title":"J Anxiety Disord"},{"key":"4195_CR53","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S0014-2999(98)00423-3","volume":"354","author":"P Tejedor-Real","year":"1998","unstructured":"Tejedor-Real P, Mico JA, Smadja C, Maldonado R, Roques BP, Gilbert-Rahola J (1998) Involvement of delta-opioid receptors in the effects induced by endogenous enkephalins on learned helplessness model. Eur J Pharmacol 354:1\u20137","journal-title":"Eur J Pharmacol"},{"key":"4195_CR54","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1038\/sj.npp.1300345","volume":"29","author":"MM Torregrossa","year":"2004","unstructured":"Torregrossa MM, Isgor C, Folk JE, Rice KC, Watson SJ, Woods JH (2004) The delta-opioid receptor agonist (+)BW373U86 regulates BDNF mRNA expression in rats. Neuropsychopharmacology 29:649\u2013659","journal-title":"Neuropsychopharmacology"},{"key":"4195_CR55","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1007\/s00213-005-0113-5","volume":"183","author":"MM Torregrossa","year":"2005","unstructured":"Torregrossa MM, Folk JE, Rice KC, Watson SJ, Woods JH (2005) Chronic administration of the delta opioid receptor agonist (+)BW373U86 and antidepressants on behavior in the forced swim test and BDNF mRNA expression in rats. Psychopharmacology Berl 183:31\u201340","journal-title":"Psychopharmacology Berl"},{"key":"4195_CR56","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.brainres.2005.11.005","volume":"1069","author":"MM Torregrossa","year":"2006","unstructured":"Torregrossa MM, Jutkiewicz EM, Mosberg HI, Balboni G, Watson SJ, Woods JH (2006) Peptidic delta opioid receptor agonists produce antidepressant-like effects in the forced swim test and regulate BDNF mRNA expression in rats. Brain Res 1069:172\u2013181","journal-title":"Brain Res"},{"key":"4195_CR57","doi-asserted-by":"publisher","first-page":"1243","DOI":"10.1056\/NEJMoa052964","volume":"354","author":"MH Trivedi","year":"2006","unstructured":"Trivedi MH, Fava M, Wisniewski SR, Thase ME, Quitkin F, Warden D, Ritz L, Nierenberg AA, Lebowitz BD, Biggs MM, Luther JF, Shores-Wilson K, Rush AJ (2006) Medication augmentation after the failure of SSRIs for depression. N Engl J Med 354:1243\u20131252","journal-title":"N Engl J Med"},{"key":"4195_CR58","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1016\/j.pnpbp.2008.11.009","volume":"33","author":"M Ventriglia","year":"2009","unstructured":"Ventriglia M, Zanardini R, Pedrini L, Placentino A, Nielsen MG, Gennarelli M, Bocchio-Chiavetto L (2009) VEGF serum levels in depressed patients during SSRI antidepressant treatment. Prog Neuropsychopharmacol Biol Psychiatry 33:146\u2013149","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"}],"container-title":["Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00213-015-4195-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00213-015-4195-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00213-015-4195-4","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00213-015-4195-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,1]],"date-time":"2025-06-01T00:50:16Z","timestamp":1748739016000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00213-015-4195-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,4]]},"references-count":58,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2016,3]]}},"alternative-id":["4195"],"URL":"https:\/\/doi.org\/10.1007\/s00213-015-4195-4","relation":{},"ISSN":["0033-3158","1432-2072"],"issn-type":[{"value":"0033-3158","type":"print"},{"value":"1432-2072","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,4]]},"assertion":[{"value":"18 August 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 December 2015","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 January 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The study was approved by the Combined Neuroscience Institutional Review Board (IRB) at the NIH. All subjects provided written informed consent before entry into the study and were assigned a Clinical Research Advocate from the NIMH Human Subjects Protection Unit to monitor the consent process and research participation throughout the study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Compliance with ethical standards"}},{"value":"The authors declare that they have no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"Funding for this work was supported in part by the Intramural Research Program at the National Institute of Mental Health, National Institutes of Health (IRP-NIMH-NIH; NCT00759395, protocol 08-M-0196), by a NARSAD Independent Investigator to Dr. Zarate, and by a Brain & Behavior Mood Disorders Research Award to Dr. Zarate. These funding sources had no further role in study design; in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the paper for publication. A patent for the use of ketamine in depression has been awarded that lists Dr. Zarate among the inventors; he has assigned his rights on the patent to the US government, but will share a percentage of any royalties that may be received by the government. Carla Maciag and Drs. Mark Smith, Thomas Hudzik, and Alan Cross were full-time employees of AstraZeneca Neuroscience Innovative Medicines at the time the study was conducted. AstraZeneca Pharmaceuticals provided the study compound.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Funding"}}]}}