{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T22:42:42Z","timestamp":1792622562130,"version":"4.5.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82030112; 82571743"],"award-info":[{"award-number":["82030112; 82571743"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["23ZR1474900"],"award-info":[{"award-number":["23ZR1474900"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012620","name":"Taishan Scholar Foundation of Shandong Province","doi-asserted-by":"publisher","award":["tsqn202312301"],"award-info":[{"award-number":["tsqn202312301"]}],"id":[{"id":"10.13039\/100012620","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Neuropsychopharmacol."],"DOI":"10.1038\/s41386-026-02549-1","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:57:15Z","timestamp":1790089035000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Kappa opioid receptor-dependent depressive-like behaviors associated with morphine withdrawal contribute to stress-induced reinstatement of morphine seeking"],"prefix":"10.1038","author":[{"given":"An-An","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan-Wen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Wen","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song-Yu","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bi-Ying","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen-Yao","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ru-Feng","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui-Ying","family":"Zan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Gen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1206-5325","authenticated-orcid":false,"given":"Yu-Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,22]]},"reference":[{"key":"2549_CR1","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1152\/physrev.00014.2018","volume":"99","author":"ND Volkow","year":"2019","unstructured":"Volkow ND, Michaelides M, Baler R. The neuroscience of drug reward and addiction. Physiol Rev. 2019;99:2115\u201340.","journal-title":"Physiol Rev"},{"key":"2549_CR2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI172883","volume":"134","author":"R Sinha","year":"2024","unstructured":"Sinha R. Stress and substance use disorders: risk, relapse, and treatment outcomes. J Clin Investig. 2024;134:e172883.","journal-title":"J Clin Investig"},{"key":"2549_CR3","doi-asserted-by":"publisher","first-page":"1417","DOI":"10.1007\/s00213-023-06370-2","volume":"240","author":"SC Monroe","year":"2023","unstructured":"Monroe SC, Radke AK. Opioid withdrawal: role in addiction and neural mechanisms. Psychopharmacology. 2023;240:1417\u201333.","journal-title":"Psychopharmacology"},{"key":"2549_CR4","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109913","volume":"37","author":"G-Y Zan","year":"2021","unstructured":"Zan G-Y, Wang Y-J, Li X-P, Fang J-F, Yao S-Y, Du J-Y, et al. Amygdalar \u03ba-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence. Cell Rep. 2021;37:109913.","journal-title":"Cell Rep"},{"key":"2549_CR5","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3109\/10826089109063460","volume":"27","author":"JE Powell","year":"1992","unstructured":"Powell JE, Taylor D. Anger, depression, and anxiety following heroin withdrawal. Int J Addict. 1992;27:25\u201335.","journal-title":"Int J Addict"},{"key":"2549_CR6","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1001\/archpsyc.55.3.259","volume":"55","author":"SF Greenfield","year":"1998","unstructured":"Greenfield SF, Weiss RD, Muenz LR, Vagge LM, Kelly JF, Bello LR, et al. The effect of depression on return to drinking: a prospective study. Arch Gen Psychiatry. 1998;55:259\u201365.","journal-title":"Arch Gen Psychiatry"},{"key":"2549_CR7","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/0165-0327(96)00068-7","volume":"41","author":"DS Hasin","year":"1996","unstructured":"Hasin DS, Tsai WY, Endicott J, Mueller TI, Coryell W, Keller M. Five-year course of major depression: effects of comorbid alcoholism. J Affect Disord. 1996;41:63\u201370.","journal-title":"J Affect Disord"},{"key":"2549_CR8","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.brainres.2009.09.074","volume":"1314","author":"AT Knoll","year":"2010","unstructured":"Knoll AT, Carlezon WA. Dynorphin, stress, and depression. Brain Res. 2010;1314:56\u201373.","journal-title":"Brain Res"},{"key":"2549_CR9","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1007\/s00213-013-3195-5","volume":"229","author":"A Van\u2019T Veer","year":"2013","unstructured":"Van\u2019T Veer A, Carlezon WA. Role of kappa-opioid receptors in stress and anxiety-related behavior. Psychopharmacology. 2013;229:435\u201352.","journal-title":"Psychopharmacology"},{"key":"2549_CR10","doi-asserted-by":"publisher","first-page":"2623","DOI":"10.1038\/npp.2013.171","volume":"38","author":"VI Chefer","year":"2013","unstructured":"Chefer VI, B\u00e4ckman CM, Gigante ED, Shippenberg TS. Kappa opioid receptors on dopaminergic neurons are necessary for kappa-mediated place aversion. Neuropsychopharmacology. 2013;38:2623\u201331.","journal-title":"Neuropsychopharmacology"},{"key":"2549_CR11","doi-asserted-by":"crossref","unstructured":"Chen Y, Guo L-B, Zan G-Y, Xu C, Yao S-Y, Wu S, et al. Astroglial kappa opioid receptor-mediated reduction of glutamate exchanger xCT in the prelimbic cortex underlies chronic stress-induced depressive-like behaviors. Mol Psychiatry. 2026;31:2991\u20133009.","DOI":"10.1038\/s41380-025-03441-y"},{"key":"2549_CR12","doi-asserted-by":"publisher","first-page":"12917","DOI":"10.1523\/JNEUROSCI.2444-15.2015","volume":"35","author":"JM Ehrich","year":"2015","unstructured":"Ehrich JM, Messinger DI, Knakal CR, Kuhar JR, Schattauer SS, Bruchas MR, et al. Kappa opioid receptor-induced aversion requires p38 MAPK activation in VTA dopamine neurons. J Neurosci J Soc Neurosci. 2015;35:12917\u201331.","journal-title":"J Neurosci J Soc Neurosci"},{"key":"2549_CR13","doi-asserted-by":"publisher","first-page":"4125","DOI":"10.1016\/j.neuron.2022.09.024","volume":"110","author":"MB Pomrenze","year":"2022","unstructured":"Pomrenze MB, Cardozo Pinto DF, Neumann PA, Llorach P, Tucciarone JM, Morishita W, et al. Modulation of 5-HT release by dynorphin mediates social deficits during opioid withdrawal. Neuron. 2022;110:4125\u2013414.e6.","journal-title":"Neuron"},{"key":"2549_CR14","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1016\/j.neuron.2025.03.018","volume":"113","author":"Q Sun","year":"2025","unstructured":"Sun Q, Liu M, Guan W, Xiao X, Dong C, Bruchas MR, et al. Dynorphin modulates reward-seeking actions through a pallido-amygdala cholinergic circuit. Neuron. 2025;113:1823\u201340.e8.","journal-title":"Neuron"},{"key":"2549_CR15","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.brainres.2009.08.062","volume":"1314","author":"MR Bruchas","year":"2010","unstructured":"Bruchas MR, Land BB, Chavkin C. The dynorphin\/kappa opioid system as a modulator of stress-induced and pro-addictive behaviors. Brain Res. 2010;1314:44\u201355.","journal-title":"Brain Res"},{"key":"2549_CR16","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/npp.2015.258","volume":"41","author":"C Chavkin","year":"2016","unstructured":"Chavkin C, Koob GF. Dynorphin, dysphoria, and dependence: the stress of addiction. Neuropsychopharmacology. 2016;41:373\u20134.","journal-title":"Neuropsychopharmacology"},{"key":"2549_CR17","doi-asserted-by":"publisher","first-page":"774","DOI":"10.1126\/science.3016896","volume":"233","author":"A Pfeiffer","year":"1986","unstructured":"Pfeiffer A, Brantl V, Herz A, Emrich HM. Psychotomimesis mediated by kappa opiate receptors. Science. 1986;233:774\u20136.","journal-title":"Science"},{"key":"2549_CR18","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1016\/j.pharmthera.2009.05.008","volume":"123","author":"WA Carlezon","year":"2009","unstructured":"Carlezon WA, B\u00e9guin C, Knoll AT, Cohen BM. Kappa-opioid ligands in the study and treatment of mood disorders. Pharm Ther. 2009;123:334\u201343.","journal-title":"Pharm Ther"},{"key":"2549_CR19","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1124\/jpet.102.046433","volume":"305","author":"SD Mague","year":"2003","unstructured":"Mague SD, Pliakas AM, Todtenkopf MS, Tomasiewicz HC, Zhang Y, Stevens WC, et al. Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats. J Pharm Exp Ther. 2003;305:323\u201330.","journal-title":"J Pharm Exp Ther"},{"key":"2549_CR20","doi-asserted-by":"publisher","first-page":"5674","DOI":"10.1523\/JNEUROSCI.23-13-05674.2003","volume":"23","author":"JP McLaughlin","year":"2003","unstructured":"McLaughlin JP, Marton-Popovici M, Chavkin C. Kappa opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses. J Neurosci: J Soc Neurosci. 2003;23:5674\u201383.","journal-title":"J Neurosci: J Soc Neurosci"},{"key":"2549_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-43636-x","volume":"14","author":"Y-J Wang","year":"2023","unstructured":"Wang Y-J, Zan G-Y, Xu C, Li X-P, Shu X, Yao S-Y, et al. The claustrum-prelimbic cortex circuit through dynorphin\/\u03ba-opioid receptor signaling underlies depression-like behaviors associated with social stress etiology. Nat Commun. 2023;14:7903.","journal-title":"Nat Commun"},{"key":"2549_CR22","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1007\/s00213-005-0167-4","volume":"183","author":"PM Beardsley","year":"2005","unstructured":"Beardsley PM, Howard JL, Shelton KL, Carroll FI. Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaine-seeking induced by footshock stressors vs cocaine primes and its antidepressant-like effects in rats. Psychopharmacology. 2005;183:118\u201326.","journal-title":"Psychopharmacology"},{"key":"2549_CR23","doi-asserted-by":"publisher","first-page":"2484","DOI":"10.1038\/npp.2013.151","volume":"38","author":"R Al-Hasani","year":"2013","unstructured":"Al-Hasani R, McCall JG, Foshage AM, Bruchas MR. Locus coeruleus kappa-opioid receptors modulate reinstatement of cocaine place preference through a noradrenergic mechanism. Neuropsychopharmacol: Publ Am Coll Neuropsychopharmacol. 2013;38:2484\u201397.","journal-title":"Neuropsychopharmacol: Publ Am Coll Neuropsychopharmacol"},{"key":"2549_CR24","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/npp.2015.142","volume":"41","author":"JR Mantsch","year":"2016","unstructured":"Mantsch JR, Baker DA, Funk D, L\u00ea AD, Shaham Y. Stress-induced reinstatement of drug seeking: 20 years of progress. Neuropsychopharmacol: Publ Am Coll Neuropsychopharmacol. 2016;41:335\u201356.","journal-title":"Neuropsychopharmacol: Publ Am Coll Neuropsychopharmacol"},{"key":"2549_CR25","doi-asserted-by":"publisher","first-page":"170","DOI":"10.3389\/fpsyt.2014.00170","volume":"5","author":"L Lalanne","year":"2014","unstructured":"Lalanne L, Ayranci G, Kieffer BL, Lutz P-E. The kappa opioid receptor: from addiction to depression, and back. Front Psychiatry. 2014;5:170.","journal-title":"Front Psychiatry"},{"key":"2549_CR26","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1523\/JNEUROSCI.16-05-01957.1996","volume":"16","author":"Y Shaham","year":"1996","unstructured":"Shaham Y, Rajabi H, Stewart J. Relapse to heroin-seeking in rats under opioid maintenance: the effects of stress, heroin priming, and withdrawal. J Neurosci: J Soc Neurosci. 1996;16:1957\u201363.","journal-title":"J Neurosci: J Soc Neurosci"},{"key":"2549_CR27","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1007\/BF02246300","volume":"119","author":"Y Shaham","year":"1995","unstructured":"Shaham Y, Stewart J. Stress reinstates heroin-seeking in drug-free animals: an effect mimicking heroin, not withdrawal. Psychopharmacology. 1995;119:334\u201341.","journal-title":"Psychopharmacology"},{"key":"2549_CR28","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/BF02245289","volume":"108","author":"J Stewart","year":"1992","unstructured":"Stewart J, Wise RA. Reinstatement of heroin self-administration habits: morphine prompts and naltrexone discourage renewed responding after extinction. Psychopharmacology. 1992;108:79\u201384.","journal-title":"Psychopharmacology"},{"key":"2549_CR29","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1007\/s00213-008-1414-2","volume":"203","author":"W Zhou","year":"2009","unstructured":"Zhou W, Zhang F, Liu H, Tang S, Lai M, Zhu H, et al. Effects of training and withdrawal periods on heroin seeking induced by conditioned cue in an animal of model of relapse. Psychopharmacology. 2009;203:677\u201384.","journal-title":"Psychopharmacology"},{"key":"2549_CR30","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/bs.pbr.2015.08.004","volume":"224","author":"M Venniro","year":"2016","unstructured":"Venniro M, Caprioli D, Shaham Y. Animal models of drug relapse and craving: from drug priming-induced reinstatement to incubation of craving after voluntary abstinence. Prog Brain Res. 2016;224:25\u201352.","journal-title":"Prog Brain Res"},{"key":"2549_CR31","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1253736","volume":"14","author":"GB Kaplan","year":"2023","unstructured":"Kaplan GB, Thompson BL. Neuroplasticity of the extended amygdala in opioid withdrawal and prolonged opioid abstinence. Front Pharm. 2023;14:1253736.","journal-title":"Front Pharm"},{"key":"2549_CR32","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1016\/j.biopsych.2022.01.002","volume":"91","author":"HL Haun","year":"2022","unstructured":"Haun HL, Lebonville CL, Solomon MG, Griffin WC, Lopez MF, Becker HC. Dynorphin\/kappa opioid receptor activity within the extended amygdala contributes to stress-enhanced alcohol drinking in mice. Biol Psychiatry. 2022;91:1019\u201328.","journal-title":"Biol Psychiatry"},{"key":"2549_CR33","doi-asserted-by":"publisher","first-page":"9937","DOI":"10.1523\/JNEUROSCI.0953-16.2016","volume":"36","author":"SK Nygard","year":"2016","unstructured":"Nygard SK, Hourguettes NJ, Sobczak GG, Carlezon WA, Bruchas MR. Stress-induced reinstatement of nicotine preference requires dynorphin\/kappa opioid activity in the basolateral amygdala. J Neurosci. 2016;36:9937\u201348.","journal-title":"J Neurosci"},{"key":"2549_CR34","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2023.107536","volume":"26","author":"J Zhang","year":"2023","unstructured":"Zhang J, Lu Y, Jia M, Bai Y, Sun L, Dong Z, et al. Kappa opioid receptor in nucleus accumbens regulates depressive-like behaviors following prolonged morphine withdrawal in mice. iScience. 2023;26:107536.","journal-title":"iScience"},{"key":"2549_CR35","doi-asserted-by":"publisher","DOI":"10.1172\/JCI163266","volume":"133","author":"Y Zhu","year":"2023","unstructured":"Zhu Y, Wang K, Ma T, Ji Y, Lou Y, Fu X, et al. Nucleus accumbens D1\/D2 circuits control opioid withdrawal symptoms in mice. J Clin Invest. 2023;133:e163266.","journal-title":"J Clin Invest"},{"key":"2549_CR36","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1111\/adb.12406","volume":"22","author":"T Ahmad","year":"2017","unstructured":"Ahmad T, Sun N, Lyons D, Laviolette SR. Bi-directional cannabinoid signalling in the basolateral amygdala controls rewarding and aversive emotional processing via functional regulation of the nucleus accumbens. Addict Biol. 2017;22:1218\u201331.","journal-title":"Addict Biol"},{"key":"2549_CR37","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1038\/s41380-023-02371-x","volume":"29","author":"X Guo","year":"2024","unstructured":"Guo X, Yuan Y, Su X, Cao Z, Chu C, Lei C, et al. Different projection neurons of basolateral amygdala participate in the retrieval of morphine withdrawal memory with diverse molecular pathways. Mol Psychiatry. 2024;29:793\u2013808.","journal-title":"Mol Psychiatry"},{"key":"2549_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2023.114435","volume":"448","author":"GEB Tavares","year":"2023","unstructured":"Tavares GEB, Bianchi PC, Yokoyama TS, Palombo P, Cruz FC. Involvement of cortical projections to basolateral amygdala in context-induced reinstatement of ethanol-seeking in rats. Behav Brain Res. 2023;448:114435.","journal-title":"Behav Brain Res"},{"key":"2549_CR39","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2025.106012","volume":"188","author":"J Han","year":"2025","unstructured":"Han J, Rim H, Jang H, Cai WT, Kim WY, Kim J-H. Pathway-specific regulation of amphetamine-induced conditioned place preference by chemogenetic modulation of basolateral amygdala projections to prelimbic cortex and nucleus accumbens subregions. Neurochem Int. 2025;188:106012.","journal-title":"Neurochem Int"},{"key":"2549_CR40","doi-asserted-by":"publisher","first-page":"2331","DOI":"10.1038\/s41386-021-01168-2","volume":"46","author":"AD Abraham","year":"2021","unstructured":"Abraham AD, Casello SM, Schattauer SS, Wong BA, Mizuno GO, Mahe K, et al. Release of endogenous dynorphin opioids in the prefrontal cortex disrupts cognition. Neuropsychopharmacol: Publ Am Coll Neuropsychopharmacol. 2021;46:2331\u201339.","journal-title":"Neuropsychopharmacol: Publ Am Coll Neuropsychopharmacol"},{"key":"2549_CR41","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1007\/BF00428203","volume":"85","author":"L Steru","year":"1985","unstructured":"Steru L, Chermat R, Thierry B, Simon P. The tail suspension test: a new method for screening antidepressants in mice. Psychopharmacology. 1985;85:367\u201370.","journal-title":"Psychopharmacology"},{"key":"2549_CR42","doi-asserted-by":"publisher","first-page":"1328","DOI":"10.1126\/science.3131879","volume":"240","author":"SM Sagar","year":"1988","unstructured":"Sagar SM, Sharp FR, Curran T. Expression of c-fos protein in brain: metabolic mapping at the cellular level. Science. 1988;240:1328\u201331.","journal-title":"Science"},{"key":"2549_CR43","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1111\/j.1365-2826.2008.01734.x","volume":"20","author":"KJ Kov\u00e1cs","year":"2008","unstructured":"Kov\u00e1cs KJ. Measurement of immediate-early gene activation: c-fos and beyond. J Neuroendocrinol. 2008;20:665\u201372.","journal-title":"J Neuroendocrinol"},{"key":"2549_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2020.108052","volume":"170","author":"V Neugebauer","year":"2020","unstructured":"Neugebauer V, Mazzitelli M, Cragg B, Ji G, Navratilova E, Porreca F. Amygdala, neuropeptides, and chronic pain-related affective behaviors. Neuropharmacology. 2020;170:108052.","journal-title":"Neuropharmacology"},{"key":"2549_CR45","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1124\/jpet.113.206086","volume":"346","author":"KA Patkar","year":"2013","unstructured":"Patkar KA, Wu J, Ganno ML, Singh HD, Ross NC, Rasakham K, et al. Physical presence of nor-binaltorphimine in mouse brain over 21 days after a single administration corresponds to its long-lasting antagonistic effect on \u03ba-opioid receptors. J Pharm Exp Ther. 2013;346:545\u201354.","journal-title":"J Pharm Exp Ther"},{"key":"2549_CR46","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2022.109551","volume":"238","author":"T Santo","year":"2022","unstructured":"Santo T, Campbell G, Gisev N, Martino-Burke D, Wilson J, Colledge-Frisby S, et al. Prevalence of mental disorders among people with opioid use disorder: a systematic review and meta-analysis. Drug Alcohol Depend. 2022;238:109551.","journal-title":"Drug Alcohol Depend"},{"key":"2549_CR47","doi-asserted-by":"publisher","first-page":"793","DOI":"10.1016\/j.biopsych.2004.06.037","volume":"56","author":"EV Nunes","year":"2004","unstructured":"Nunes EV, Sullivan MA, Levin FR. Treatment of depression in patients with opiate dependence. Biol Psychiatry. 2004;56:793\u2013802.","journal-title":"Biol Psychiatry"},{"key":"2549_CR48","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7620860","volume":"2016","author":"H Chalana","year":"2016","unstructured":"Chalana H, Kundal T, Gupta V, Malhari AS. Predictors of relapse after inpatient opioid detoxification during 1-year follow-up. J Addict. 2016;2016:7620860.","journal-title":"J Addict"},{"key":"2549_CR49","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1093\/fampra\/cms014","volume":"29","author":"CS Cornford","year":"2012","unstructured":"Cornford CS, Umeh K, Manshani N. Heroin users\u2019 experiences of depression: a qualitative study. Fam Pr. 2012;29:586\u201392.","journal-title":"Fam Pr"},{"key":"2549_CR50","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1124\/jpet.108.139196","volume":"326","author":"ZD Cooper","year":"2008","unstructured":"Cooper ZD, Truong YN-T, Shi Y-G, Woods JH. Morphine deprivation increases self-administration of the fast- and short-acting mu-opioid receptor agonist remifentanil in the rat. J Pharm Exp Ther. 2008;326:920\u20139.","journal-title":"J Pharm Exp Ther"},{"key":"2549_CR51","doi-asserted-by":"publisher","first-page":"790","DOI":"10.1016\/j.neuron.2012.09.040","volume":"76","author":"JP Britt","year":"2012","unstructured":"Britt JP, Benaliouad F, McDevitt RA, Stuber GD, Wise RA, Bonci A. Synaptic and behavioral profile of multiple glutamatergic inputs to the nucleus accumbens. Neuron. 2012;76:790\u2013803.","journal-title":"Neuron"},{"key":"2549_CR52","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.pscychresns.2009.03.006","volume":"173","author":"MAM Peluso","year":"2009","unstructured":"Peluso MAM, Glahn DC, Matsuo K, Monkul ES, Najt P, Zamarripa F, et al. Amygdala hyperactivation in untreated depressed individuals. Psychiatry Res: Neuroimaging. 2009;173:158\u201361.","journal-title":"Psychiatry Res: Neuroimaging"},{"key":"2549_CR53","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/j.neubiorev.2015.08.017","volume":"57","author":"KM Wassum","year":"2015","unstructured":"Wassum KM, Izquierdo A. The basolateral amygdala in reward learning and addiction. Neurosci Biobehav Rev. 2015;57:271\u201383.","journal-title":"Neurosci Biobehav Rev"},{"key":"2549_CR54","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.neuropharm.2011.06.014","volume":"62","author":"E Chartoff","year":"2012","unstructured":"Chartoff E, Sawyer A, Rachlin A, Potter D, Pliakas A, Carlezon WA. Blockade of kappa opioid receptors attenuates the development of depressive-like behaviors induced by cocaine withdrawal in rats. Neuropharmacology. 2012;62:167\u201376.","journal-title":"Neuropharmacology"},{"key":"2549_CR55","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1523\/JNEUROSCI.4458-07.2008","volume":"28","author":"BB Land","year":"2008","unstructured":"Land BB, Bruchas MR, Lemos JC, Xu M, Melief EJ, Chavkin C. The dysphoric component of stress is encoded by activation of the dynorphin kappa-opioid system. J Neurosci J Soc Neurosci. 2008;28:407\u201314.","journal-title":"J Neurosci J Soc Neurosci"},{"key":"2549_CR56","doi-asserted-by":"publisher","first-page":"19168","DOI":"10.1073\/pnas.0910705106","volume":"106","author":"BB Land","year":"2009","unstructured":"Land BB, Bruchas MR, Schattauer S, Giardino WJ, Aita M, Messinger D, et al. Activation of the kappa opioid receptor in the dorsal raphe nucleus mediates the aversive effects of stress and reinstates drug seeking. Proc Natl Acad Sci USA 2009;106:19168\u201373.","journal-title":"Proc Natl Acad Sci USA"},{"key":"2549_CR57","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.neuron.2019.03.003","volume":"102","author":"DC Castro","year":"2019","unstructured":"Castro DC, Bruchas MR. A motivational and neuropeptidergic hub: anatomical and functional diversity within the nucleus accumbens shell. Neuron. 2019;102:529\u201352.","journal-title":"Neuron"},{"key":"2549_CR58","doi-asserted-by":"publisher","first-page":"289","DOI":"10.3109\/10253890109014753","volume":"4","author":"S Erb","year":"2001","unstructured":"Erb S, Shaham Y, Stewart J. Stress-induced relapse to drug seeking in the rat: role of the bed nucleus of the stria terminalis and amygdala. Stress. 2001;4:289\u2013303.","journal-title":"Stress"},{"key":"2549_CR59","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1038\/s41386-018-0125-6","volume":"44","author":"JB Becker","year":"2019","unstructured":"Becker JB, Chartoff E. Sex differences in neural mechanisms mediating reward and addiction. Neuropsychopharmacol: Publ Am Coll Neuropsychopharmacol. 2019;44:166\u201383.","journal-title":"Neuropsychopharmacol: Publ Am Coll Neuropsychopharmacol"},{"key":"2549_CR60","doi-asserted-by":"publisher","first-page":"466","DOI":"10.3389\/fnins.2015.00466","volume":"9","author":"EH Chartoff","year":"2015","unstructured":"Chartoff EH, Mavrikaki M. Sex differences in kappa opioid receptor function and their potential impact on addiction. Front Neurosci. 2015;9:466.","journal-title":"Front Neurosci"}],"container-title":["Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02549-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02549-1","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02549-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:03:03Z","timestamp":1790092983000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41386-026-02549-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,22]]},"references-count":60,"alternative-id":["2549"],"URL":"https:\/\/doi.org\/10.1038\/s41386-026-02549-1","relation":{},"ISSN":["0893-133X","1740-634X"],"issn-type":[{"value":"0893-133X","type":"print"},{"value":"1740-634X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,22]]},"assertion":[{"value":"5 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 August 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 August 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 September 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}