{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:15:53Z","timestamp":1791807353843,"version":"4.3.4"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2023,7,1]],"date-time":"2023-07-01T00:00:00Z","timestamp":1688169600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2023,5,5]],"date-time":"2023-05-05T00:00:00Z","timestamp":1683244800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"Narodowym Centrum Nauki","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004281","name":"National Science Centre Poland","doi-asserted-by":"publisher","award":["2019\/33\/N\/NZ7\/02378"],"award-info":[{"award-number":["2019\/33\/N\/NZ7\/02378"]}],"id":[{"id":"10.13039\/501100004281","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":[[2023,7]]},"DOI":"10.1016\/j.bbr.2023.114466","type":"journal-article","created":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T20:54:17Z","timestamp":1683147257000},"page":"114466","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["The differential influence of PZM21, a nonrewarding \u03bc-opioid receptor agonist with G protein bias, on behavioural despair and fear response in mice"],"prefix":"10.1016","volume":"449","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3573-3533","authenticated-orcid":false,"given":"Lucja","family":"Szumiec","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryszard","family":"Bugno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukasz","family":"Szumiec","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryszard","family":"Przewlocki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bbr.2023.114466_bib1","doi-asserted-by":"crossref","DOI":"10.1016\/j.peptides.2020.170348","article-title":"Endogenous opiates and behavior: 2018","volume":"132","author":"Bodnar","year":"2020","journal-title":"Peptides"},{"key":"10.1016\/j.bbr.2023.114466_bib2","series-title":"Horm. Brain Behav.","first-page":"225","article-title":"1.08 - Stress and opioid systems","author":"Przewlocki","year":"2017"},{"key":"10.1016\/j.bbr.2023.114466_bib3","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.pnpbp.2018.08.011","article-title":"The opioid system in stress-induced memory disorders: from basic mechanisms to clinical implications in post-traumatic stress disorder and Alzheimer\u2019s disease","volume":"88","author":"Torres-Berrio","year":"2019","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"10.1016\/j.bbr.2023.114466_bib4","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41380-018-0117-2","article-title":"Endogenous opioid system dysregulation in depression: implications for new therapeutic approaches","volume":"24","author":"Peci\u00f1a","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"10.1016\/j.bbr.2023.114466_bib5","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.neulet.2005.02.026","article-title":"Evidence for the involvement of the opioid system in the agmatine antidepressant-like effect in the forced swimming test","volume":"381","author":"Zomkowski","year":"2005","journal-title":"Neurosci. Lett."},{"key":"10.1016\/j.bbr.2023.114466_bib6","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1017\/S1461145711001842","article-title":"Active behaviours produced by antidepressants and opioids in the mouse tail suspension test","volume":"16","author":"Berrocoso","year":"2013","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"10.1016\/j.bbr.2023.114466_bib7","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1038\/sj.npp.1301149","article-title":"Antidepressant-like effect of endomorphin-1 and endomorphin-2 in mice","volume":"32","author":"Fichna","year":"2007","journal-title":"Neuropsychopharmacol. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"10.1016\/j.bbr.2023.114466_bib8","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1007\/BF02246283","article-title":"Effects of morphine, naloxone and their interaction in the learned-helplessness paradigm in rats","volume":"123","author":"Besson","year":"1996","journal-title":"Psychopharmacol. (Berl.)"},{"key":"10.1016\/j.bbr.2023.114466_bib9","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/0091-3057(95)00067-7","article-title":"Implication of endogenous opioid system in the learned helplessness model of depression","volume":"52","author":"Tejedor-Real","year":"1995","journal-title":"Pharm. Biochem Behav."},{"key":"10.1016\/j.bbr.2023.114466_bib10","series-title":"Encycl. Psychopharmacol.","first-page":"1","article-title":"Behavioral despair","author":"Lucki","year":"2010"},{"key":"10.1016\/j.bbr.2023.114466_bib11","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1111\/j.1749-6632.1982.tb39483.x","article-title":"Possible antidepressive effects of opioids: action of buprenorphine","volume":"398","author":"Emrich","year":"1982","journal-title":"Ann. N. Y Acad. Sci."},{"key":"10.1016\/j.bbr.2023.114466_bib12","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ajp.2017.01.015","article-title":"Use of Buprenorphine in treatment of refractory depression\u2014a review of current literature","volume":"26","author":"Stanciu","year":"2017","journal-title":"Asian J. Psychiatry"},{"key":"10.1016\/j.bbr.2023.114466_bib13","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1038\/npp.2017.60","article-title":"The behavioral effects of the antidepressant tianeptine require the Mu-opioid receptor","volume":"42","author":"Samuels","year":"2017","journal-title":"Neuropsychopharmacol. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"10.1016\/j.bbr.2023.114466_bib14","doi-asserted-by":"crossref","first-page":"2656","DOI":"10.1073\/pnas.1916570117","article-title":"Opioid system is necessary but not sufficient for antidepressive actions of ketamine in rodents","volume":"117","author":"Klein","year":"2020","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.bbr.2023.114466_bib15","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1038\/s41386-021-01192-2","article-title":"Mu opioid receptors on hippocampal GABAergic interneurons are critical for the antidepressant effects of tianeptine","volume":"47","author":"Han","year":"2022","journal-title":"Neuropsychopharmacol. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"10.1016\/j.bbr.2023.114466_bib16","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.jad.2020.12.051","article-title":"The relationship between early administration of morphine or nitrous oxide gas and PTSD symptom development","volume":"281","author":"Deforges","year":"2021","journal-title":"J. Affect Disord."},{"key":"10.1016\/j.bbr.2023.114466_bib17","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1016\/j.biopsych.2008.10.032","article-title":"A study of the protective function of acute morphine administration on subsequent posttraumatic stress disorder","volume":"65","author":"Bryant","year":"2009","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.bbr.2023.114466_bib18","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1097\/00004583-200108000-00013","article-title":"Relationship between acute morphine and the course of PTSD in children with burns","volume":"40","author":"Saxe","year":"2001","journal-title":"J. Am. Acad. Child Adolesc. Psychiatry"},{"key":"10.1016\/j.bbr.2023.114466_bib19","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1016\/j.brat.2010.05.002","article-title":"Predictors of posttraumatic stress in children following injury: the influence of appraisals, heart rate, and morphine use","volume":"48","author":"Nixon","year":"2010","journal-title":"Behav. Res Ther."},{"key":"10.1016\/j.bbr.2023.114466_bib20","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1056\/NEJMoa0903326","article-title":"Morphine use after combat injury in Iraq and post-traumatic stress disorder","volume":"362","author":"Holbrook","year":"2010","journal-title":"N. Engl. J. Med"},{"key":"10.1016\/j.bbr.2023.114466_bib21","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.bbr.2015.06.001","article-title":"Opioid-dependent regulation of high and low fear responses in two inbred mouse strains","volume":"292","author":"Szklarczyk","year":"2015","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.bbr.2023.114466_bib22","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.pnpbp.2019.04.001","article-title":"Fear memory-induced alterations in the mRNA expression of G proteins in the mouse brain and the impact of immediate posttraining treatment with morphine","volume":"93","author":"Zelek-Molik","year":"2019","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"10.1016\/j.bbr.2023.114466_bib23","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1016\/j.pbb.2012.10.013","article-title":"Morphine prevents the development of stress-enhanced fear learning","volume":"103","author":"Szczytkowski-Thomson","year":"2013","journal-title":"Pharm. Biochem Behav."},{"key":"10.1016\/j.bbr.2023.114466_bib24","doi-asserted-by":"crossref","first-page":"11754","DOI":"10.3390\/ijerph191811754","article-title":"Opioid misuse: a review of the main issues, challenges, and strategies","volume":"19","author":"Biancuzzi","year":"2022","journal-title":"Int. J. Environ. Res Public Health"},{"key":"10.1016\/j.bbr.2023.114466_bib25","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.biopsych.2019.10.020","article-title":"Toward directing opioid receptor signaling to refine opioid therapeutics","volume":"87","author":"Grim","year":"2020","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.bbr.2023.114466_bib26","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nature19112","article-title":"Structure-based discovery of opioid analgesics with reduced side effects","volume":"537","author":"Manglik","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.bbr.2023.114466_bib27","doi-asserted-by":"crossref","first-page":"4434","DOI":"10.1111\/bph.14805","article-title":"Functional characterization of a novel opioid, PZM21, and its effects on the behavioural responses to morphine","volume":"176","author":"Kudla","year":"2019","journal-title":"Br. J. Pharm."},{"key":"10.1016\/j.bbr.2023.114466_bib28","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.neuroscience.2014.11.035","article-title":"Behavioral and molecular alterations in mice resulting from chronic treatment with dexamethasone: relevance to depression","volume":"286","author":"Skupio","year":"2015","journal-title":"Neuroscience"},{"key":"10.1016\/j.bbr.2023.114466_bib29","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1038\/266730a0","article-title":"Depression: a new animal model sensitive to antidepressant treatments","volume":"266","author":"Porsolt","year":"1977","journal-title":"Nature"},{"key":"10.1016\/j.bbr.2023.114466_bib30","doi-asserted-by":"crossref","DOI":"10.1016\/j.bbr.2020.113095","article-title":"Knockdown of the astrocytic glucocorticoid receptor in the central nucleus of the amygdala diminishes conditioned fear expression and anxiety","volume":"402","author":"Wiktorowska","year":"2021","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.bbr.2023.114466_bib31","doi-asserted-by":"crossref","first-page":"11981","DOI":"10.1073\/pnas.0801329105","article-title":"Enhanced contextual fear memory in central serotonin-deficient mice","volume":"105","author":"Dai","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.bbr.2023.114466_bib32","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.tins.2012.11.002","article-title":"Opioid receptors: distinct roles in mood disorders","volume":"36","author":"Lutz","year":"2013","journal-title":"Trends Neurosci."},{"key":"10.1016\/j.bbr.2023.114466_bib33","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.neubiorev.2010.06.006","article-title":"Reconsidering anhedonia in depression: lessons from translational neuroscience","volume":"35","author":"Treadway","year":"2011","journal-title":"Neurosci. Biobehav Rev."},{"key":"10.1016\/j.bbr.2023.114466_bib34","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1080\/10550880802122646","article-title":"Psychotherapeutic benefits of opioid agonist therapy","volume":"27","author":"Tenore","year":"2008","journal-title":"J. Addict. Dis."},{"key":"10.1016\/j.bbr.2023.114466_bib35","doi-asserted-by":"crossref","first-page":"1612","DOI":"10.2174\/138161209788168100","article-title":"Opiates as antidepressants","volume":"15","author":"Berrocoso","year":"2009","journal-title":"Curr. Pharm. Des."},{"key":"10.1016\/j.bbr.2023.114466_bib36","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1097\/JCP.0000000000001311","article-title":"Rapid improvement of treatment-resistant major depression during the administration of low-dose oxycodone","volume":"41","author":"Magen","year":"2021","journal-title":"J. Clin. Psychopharmacol."},{"key":"10.1016\/j.bbr.2023.114466_bib37","unstructured":"Commissioner O of the. Tianeptine Products Linked to Serious Harm, Overdoses, Death. FDA. 2022. 2 October 2022."},{"key":"10.1016\/j.bbr.2023.114466_bib38","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1038\/s41386-020-0738-4","article-title":"Selective kappa-opioid antagonism ameliorates anhedonic behavior: evidence from the fast-fail trial in mood and anxiety spectrum disorders (FAST-MAS)","volume":"45","author":"Pizzagalli","year":"2020","journal-title":"Neuropsychopharmacology"},{"key":"10.1016\/j.bbr.2023.114466_bib39","doi-asserted-by":"crossref","first-page":"10908","DOI":"10.1073\/pnas.95.18.10908","article-title":"Selectively enhanced contextual fear conditioning in mice lacking the transcriptional regulator CCAAT\/enhancer binding protein \u03b4","volume":"95","author":"Sterneck","year":"1998","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.bbr.2023.114466_bib40","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1037\/0735-7044.106.2.274","article-title":"Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning","volume":"106","author":"Phillips","year":"1992","journal-title":"Behav. Neurosci."},{"key":"10.1016\/j.bbr.2023.114466_bib41","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1038\/s41386-022-01294-5","article-title":"A novel role for the lateral habenula in fear learning","volume":"47","author":"Sachella","year":"2022","journal-title":"Neuropsychopharmacol. Publ. Am. Coll. Neuropsychopharmacol."},{"key":"10.1016\/j.bbr.2023.114466_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.addbeh.2021.107026","article-title":"Treatment outcomes in individuals diagnosed with comorbid opioid use disorder and Posttraumatic stress disorder: a review","volume":"122","author":"Meshberg-Cohen","year":"2021","journal-title":"Addict. Behav."},{"key":"10.1016\/j.bbr.2023.114466_bib43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jad.2016.12.043","article-title":"The role of \u03b2-arrestin-2 on Fear\/anxious-related memory in a rat model of Post-traumatic stress disorder","volume":"213","author":"Ding","year":"2017","journal-title":"J. Affect Disord."},{"key":"10.1016\/j.bbr.2023.114466_bib44","doi-asserted-by":"crossref","first-page":"8177","DOI":"10.1523\/JNEUROSCI.20-21-08177.2000","article-title":"Activation of ERK\/MAP kinase in the amygdala is required for memory consolidation of pavlovian fear conditioning","volume":"20","author":"Schafe","year":"2000","journal-title":"J. Neurosci."},{"key":"10.1016\/j.bbr.2023.114466_bib45","doi-asserted-by":"crossref","first-page":"eaba0245","DOI":"10.1126\/scisignal.aba0245","article-title":"\u03b2-Arrestin\u2013dependent ERK signaling reduces anxiety-like and conditioned fear\u2013related behaviors in mice","volume":"14","author":"Ko","year":"2021","journal-title":"Sci. Signal"},{"issue":"2","key":"10.1016\/j.bbr.2023.114466_bib46","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1213\/ANE.0000000000003360","article-title":"Pharmacological characterization of levorphanol, a G-protein biased opioid analgesic","volume":"128","author":"Le Rouzic","year":"2019","journal-title":"Anesth Analg"},{"key":"10.1016\/j.bbr.2023.114466_bib47","doi-asserted-by":"crossref","first-page":"55","DOI":"10.3390\/pharmaceutics14010055","article-title":"Comparison of an addictive potential of \u03bc-opioid receptor agonists with G protein bias: behavioral and molecular modeling studies","volume":"14","author":"Kudla","year":"2021","journal-title":"Pharmaceutics"}],"container-title":["Behavioural Brain Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0166432823001845?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0166432823001845?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T13:38:22Z","timestamp":1759066702000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0166432823001845"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7]]},"references-count":47,"alternative-id":["S0166432823001845"],"URL":"https:\/\/doi.org\/10.1016\/j.bbr.2023.114466","relation":{},"ISSN":["0166-4328"],"issn-type":[{"value":"0166-4328","type":"print"}],"subject":[],"published":{"date-parts":[[2023,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The differential influence of PZM21, a nonrewarding \u03bc-opioid receptor agonist with G protein bias, on behavioural despair and fear response in mice","name":"articletitle","label":"Article Title"},{"value":"Behavioural Brain Research","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bbr.2023.114466","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2023 The Authors. Published by Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"114466"}}