{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T05:00:36Z","timestamp":1784782836648,"version":"3.55.0"},"reference-count":83,"publisher":"Springer Science and Business Media LLC","issue":"10","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"DOI":"10.13039\/501100004048","name":"Kashan University of Medical Sciences","doi-asserted-by":"publisher","award":["401181"],"award-info":[{"award-number":["401181"]}],"id":[{"id":"10.13039\/501100004048","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1007\/s00210-026-05222-y","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T03:06:14Z","timestamp":1776913574000},"page":"15241-15254","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The effect of clavulanic acid on the development of tolerance and dependence induced by morphine in mice: role of DRD2 and NR1 genes, oxidative stress, and GDNF protein"],"prefix":"10.1007","volume":"399","author":[{"given":"Peyman","family":"Esmaili-Shahzade-Ali-Akbari","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Behrang","family":"Alani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elahe Seyed","family":"Hosseini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamid Reza","family":"Banafshe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abolfazl","family":"Ardjmand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammadreza Rashidi","family":"Nooshabadi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abbas","family":"Haghparast","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9193-6039","authenticated-orcid":false,"given":"Amir","family":"Ghaderi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"5222_CR1","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.bbr.2013.02.034","volume":"2247","author":"AO Abdel-Zaher","year":"2013","unstructured":"Abdel-Zaher AO, Mostafa MG, Farghaly HSM, Hamdy MM, Abdel-Hady RH (2013) Role of oxidative stress and inducible nitric oxide synthase in morphine-induced tolerance and dependence in mice. Effect of alpha-lipoic acid. Behav Brain Res 2247:17\u201326","journal-title":"Behav Brain Res"},{"issue":"1\u20133","key":"5222_CR2","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1016\/j.ejphar.2013.01.036","volume":"702","author":"AO Abdel-Zaher","year":"2013","unstructured":"Abdel-Zaher AO, Mostafa MG, Farghly HM, Hamdy MM, Omran GA, Al-Shaibani NKM (2013) Inhibition of brain oxidative stress and inducible nitric oxide synthase expression by thymoquinone attenuates the development of morphine tolerance and dependence in mice. Eur J Pharmacol 702(1\u20133):62\u201370","journal-title":"Eur J Pharmacol"},{"issue":"5","key":"5222_CR3","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1111\/j.1471-4159.1992.tb10033.x","volume":"58","author":"E Acquas","year":"1992","unstructured":"Acquas E, Di Chiara G (1992) Depression of mesolimbic dopamine transmission and sensitization to morphine during opiate abstinence. J Neurochem 58(5):1620\u20131625","journal-title":"J Neurochem"},{"issue":"3","key":"5222_CR4","doi-asserted-by":"publisher","first-page":"241","DOI":"10.15412\/J.BCN.03070309","volume":"7","author":"S Ahmadi","year":"2016","unstructured":"Ahmadi S, Rafieenia F, Rostamzadeh J (2016) Morphine-induced analgesic tolerance effect on gene expression of the NMDA receptor subunit 1 in rat striatum and prefrontal cortex. Basic Clin Neurosci J 7(3):241","journal-title":"Basic Clin Neurosci J"},{"key":"5222_CR5","doi-asserted-by":"crossref","unstructured":"Ahmadi SA, Khanizad AK, Fotouhi SF (2022) Increases in pro-inflammatory cytokines in the ventral striatum following frequent morphine exposure impose new setpoints in the expression of biologically-relevant genes to addiction and neuroinflammation in rats. Jentashapir J Cell Mol Biol 13(4):e132286. Available from: https:\/\/brieflands.com\/articles\/jjcmb-132286.bib","DOI":"10.5812\/jjcmb-132286"},{"key":"5222_CR6","doi-asserted-by":"publisher","first-page":"617","DOI":"10.1134\/S000635090905011X","volume":"54","author":"AV Alekseenko","year":"2009","unstructured":"Alekseenko AV, Kolos VA, Waseem TV, Fedorovich SV (2009) Glutamate induces formation of free radicals in rat brain synaptosomes. Biophysics (Oxf) 54:617\u2013620","journal-title":"Biophysics (Oxf)"},{"issue":"5","key":"5222_CR7","doi-asserted-by":"publisher","first-page":"e2975","DOI":"10.1002\/brb3.2975","volume":"13","author":"ZM Arani","year":"2023","unstructured":"Arani ZM, Heidariyeh N, Ghavipanjeh G, Lotfinia M, Banafshe HR (2023) Effect of risperidone on morphine\u2010induced conditioned place preference and dopamine receptor D2 gene expression in male rat hippocampus. Brain Behav 13(5):e2975. https:\/\/doi.org\/10.1002\/brb3.2975","journal-title":"Brain Behav [internet]"},{"issue":"2","key":"5222_CR8","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1111\/j.1476-5381.1972.tb06866.x","volume":"46","author":"M Babbini","year":"1972","unstructured":"Babbini M, Davis WM (1972) Time-dose relationships for locomotor activity effects of morphine after acute or repeated treatment. Br J Pharmacol 46(2):213","journal-title":"Br J Pharmacol"},{"issue":"1","key":"5222_CR9","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.coph.2004.08.012","volume":"5","author":"CP Bailey","year":"2005","unstructured":"Bailey CP, Connor M (2005) Opioids: cellular mechanisms of tolerance and physical dependence. Curr Opin Pharmacol 5(1):60\u201368","journal-title":"Curr Opin Pharmacol"},{"key":"5222_CR10","unstructured":"Banani A, Maleki-Dizaji N, Garjani A, Soraya H, Mostafalou S, Ziaee M (2012) Clavulanic acid exhibits anti-inflammatory effects on carrageenan-induced paw edema model of inflammation in rats.\u00a0Ann Biol Res 3(7):3312\u20133320"},{"issue":"1","key":"5222_CR11","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1124\/pr.110.002642","volume":"63","author":"JM Beaulieu","year":"2011","unstructured":"Beaulieu JM, Gainetdinov RR, Sibley DR (2011) The physiology, signaling, and pharmacology of dopamine receptors. Pharmacol Rev 63(1):182\u2013217","journal-title":"Pharmacol Rev"},{"key":"5222_CR12","doi-asserted-by":"publisher","unstructured":"Berr\u00edos-C\u00e1rcamo P, Quezada M, Quintanilla ME, Morales P, Ezquer M, Herrera-Marschitz M et al (2020) Oxidative stress and neuroinflammation as a pivot in drug abuse. A focus on the therapeutic potential of antioxidant and anti-inflammatory agents and biomolecules. Antioxidants (Basel) 9(9):830. https:\/\/doi.org\/10.3390\/antiox9090830","DOI":"10.3390\/antiox9090830"},{"key":"5222_CR13","doi-asserted-by":"publisher","unstructured":"Binneto\u011flu D, Ar\u0131c\u0131o\u011flu F, \u00d6zcan H, Okkay U, Hac\u0131m\u00fcft\u00fco\u011flu A (2019) Antidepressant-like effects of ceftriaxone in chronic unpredictable mild stress model in rats: the importance of reuptake time of glutamate. Clin Exp Heal Sci. https:\/\/doi.org\/10.33808\/clinexphealthsci.613963","DOI":"10.33808\/clinexphealthsci.613963"},{"issue":"2","key":"5222_CR14","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/0006-8993(84)90239-7","volume":"302","author":"JJ Bouyer","year":"1984","unstructured":"Bouyer JJ, Park DH, Joh TH, Pickel VM (1984) Chemical and structural analysis of the relation between cortical inputs and tyrosine hydroxylase-containing terminals in rat neostriatum. Brain Res 302(2):267\u2013275","journal-title":"Brain Res"},{"issue":"3","key":"5222_CR15","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/0091-3057(81)90403-2","volume":"14","author":"LS Brady","year":"1981","unstructured":"Brady LS, Holtzman SG (1981) Locomotor activity in morphine-dependent and post-dependent rats. Pharmacol Biochem Behav 14(3):361\u2013370","journal-title":"Pharmacol Biochem Behav"},{"key":"5222_CR16","first-page":"1151","volume-title":"Goodman and Gilman\u2019s the pharmacological basis of therapeutics","author":"L Brunton","year":"2006","unstructured":"Brunton L, Lazo J, Parker K (2006) Goodman and Gilman\u2019s the pharmacological basis of therapeutics, 11th ed. McGraw-Hill Company, New York, pp 1151\u20131152","edition":"11th ed"},{"key":"5222_CR17","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.cobeha.2016.12.003","volume":"13","author":"CM Cahill","year":"2017","unstructured":"Cahill CM, Taylor AM (2017) Neuroinflammation-a co-occurring phenomenon linking chronic pain and opioid dependence. Curr Opin Behav Sci 13:171\u2013177","journal-title":"Curr Opin Behav Sci"},{"issue":"1","key":"5222_CR18","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.pharmthera.2008.12.001","volume":"122","author":"S Carnicella","year":"2009","unstructured":"Carnicella S, Ron D (2009) GDNF--a potential target to treat addiction. Pharmacol Ther 122(1):9\u201318","journal-title":"Pharmacol Ther"},{"issue":"1\u20133","key":"5222_CR19","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.ejphar.2009.03.009","volume":"609","author":"JSW Chan","year":"2009","unstructured":"Chan JSW, Kim DJ, Ahn CH, Oosting RS, Olivier B (2009) Clavulanic acid stimulates sexual behaviour in male rats. Eur J Pharmacol 609(1\u20133):69\u201373","journal-title":"Eur J Pharmacol"},{"issue":"13","key":"5222_CR20","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.2174\/13895575113139990074","volume":"13","author":"J Chen","year":"2013","unstructured":"Chen J, Shang X, Hu F, Lao X, Gao X, Zheng H et al (2013) \u03b2-Lactamase inhibitors: an update. Mini Rev Med Chem 13(13):1846\u20131861","journal-title":"Mini Rev Med Chem"},{"key":"5222_CR21","volume":"9","author":"X d\u2019Anglemont de Tassigny","year":"2015","unstructured":"d\u2019Anglemont de Tassigny X, Pascual A, L\u00f3pez-Barneo J (2015) GDNF-based therapies, GDNF-producing interneurons, and trophic support of the dopaminergic nigrostriatal pathway. Implications for Parkinson\u2019s disease. Front Neuroanat 9:10","journal-title":"Front Neuroanat"},{"key":"5222_CR22","volume":"9","author":"MS D\u2019Souza","year":"2015","unstructured":"D\u2019Souza MS (2015) Glutamatergic transmission in drug reward: implications for drug addiction. Front Neurosci 9:404","journal-title":"Front Neurosci"},{"issue":"1","key":"5222_CR23","doi-asserted-by":"publisher","first-page":"38746","DOI":"10.1038\/srep38746","volume":"6","author":"WL Dai","year":"2016","unstructured":"Dai WL, Xiong F, Yan B, Cao ZY, Liu WT, Liu JH et al (2016) Blockade of neuronal dopamine D2 receptor attenuates morphine tolerance in mice spinal cord. Sci Rep 6(1):38746","journal-title":"Sci Rep"},{"issue":"1","key":"5222_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/s12954-018-0272-4","volume":"16","author":"I Delargy","year":"2019","unstructured":"Delargy I, Crowley D, Van Hout MC (2019) Twenty years of the methadone treatment protocol in Ireland: reflections on the role of general practice. Harm Reduct J 16(1):5","journal-title":"Harm Reduct J"},{"issue":"2","key":"5222_CR25","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/S0022-3565(24)39103-7","volume":"294","author":"JP Druhan","year":"2000","unstructured":"Druhan JP, Walters CL, Aston-Jones G (2000) Behavioral activation induced by D2-like receptor stimulation during opiate withdrawal. J Pharmacol Exp Ther 294(2):531\u2013538","journal-title":"J Pharmacol Exp Ther"},{"key":"5222_CR26","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.neuro.2021.02.005","volume":"84","author":"P Esmaili-Shahzade-Ali-Akbari","year":"2021","unstructured":"Esmaili-Shahzade-Ali-Akbari P, Hosseinzadeh H, Mehri S (2021) Effect of suvorexant on morphine tolerance and dependence in mice: role of NMDA, AMPA, ERK and CREB proteins. Neurotoxicology 84:64\u201372","journal-title":"Neurotoxicology"},{"key":"5222_CR27","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.22110","author":"P Esmaili-Shahzade-Ali-Akbari","year":"2023","unstructured":"Esmaili-Shahzade-Ali-Akbari P, Ghaderi A, Hosseini SMM, Nejat F, Saeedi-Mofrad M, Karimi-Houyeh M et al (2023) \u03b2_lactam antibiotics against drug addiction: a novel therapeutic option. Drug Dev Res. https:\/\/doi.org\/10.1002\/ddr.22110","journal-title":"Drug Dev Res"},{"issue":"2","key":"5222_CR28","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/bjp.2008.51","volume":"154","author":"MW Feltenstein","year":"2008","unstructured":"Feltenstein MW, See RE (2008) The neurocircuitry of addiction: an overview. Br J Pharmacol 154(2):261\u2013274. https:\/\/doi.org\/10.1038\/bjp.2008.51","journal-title":"Br J Pharmacol"},{"key":"5222_CR29","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.physbeh.2015.06.009","volume":"149","author":"CS Freet","year":"2015","unstructured":"Freet CS, Lawrence AL (2015) Ceftriaxone attenuates acquisition and facilitates extinction of cocaine-induced suppression of saccharin intake in C57BL\/6J mice. Physiol Behav 149:174\u2013180","journal-title":"Physiol Behav"},{"key":"5222_CR30","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252011136","author":"AR Galambos","year":"2024","unstructured":"Galambos AR, Essmat N, Lakatos PP, Sz\u00fccs E, Boldizs\u00e1r I, Abbood SK et al (2024) Glycine transporter 1 inhibitors minimize the analgesic tolerance to morphine. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms252011136","journal-title":"Int J Mol Sci"},{"issue":"2","key":"5222_CR31","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/j.neubiorev.2009.11.009","volume":"35","author":"UE Ghitza","year":"2010","unstructured":"Ghitza UE, Zhai H, Wu P, Airavaara M, Shaham Y, Lu L (2010) Role of BDNF and GDNF in drug reward and relapse: a review. Neurosci Biobehav Rev 35(2):157\u2013171","journal-title":"Neurosci Biobehav Rev"},{"key":"5222_CR32","doi-asserted-by":"crossref","unstructured":"Guo Y, Wang HL, Xiang XH, Zhao Y (2009) The role of glutamate and its receptors in mesocorticolimbic dopaminergic regions in opioid addiction. Neurosci Biobehav Rev 33(6):864\u2013873. Available from: http:\/\/www.sciencedirect.com\/science\/article\/pii\/S0149763409000219","DOI":"10.1016\/j.neubiorev.2009.02.005"},{"key":"5222_CR33","doi-asserted-by":"crossref","unstructured":"Guo Y, Wang HLL, Xiang XHH, Zhao Y (2009) The role of glutamate and its receptors in mesocorticolimbic dopaminergic regions in opioid addiction. Neurosci Biobehav Rev 33(6):864\u2013873. Available from: http:\/\/www.sciencedirect.com\/science\/article\/pii\/S0149763409000219","DOI":"10.1016\/j.neubiorev.2009.02.005"},{"issue":"5","key":"5222_CR34","first-page":"315","volume":"9","author":"V Hajhashemi","year":"2014","unstructured":"Hajhashemi V, Dehdashti K (2014) Antinociceptive effect of clavulanic acid and its preventive activity against development of morphine tolerance and dependence in animal models. Res Pharm Sci 9(5):315\u2013321","journal-title":"Res Pharm Sci"},{"issue":"6493","key":"5222_CR35","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/371155a0","volume":"371","author":"GC Harris","year":"1994","unstructured":"Harris GC, Aston-Jones G (1994) Involvement of D2 dopamine receptors in the nucleus accumbens in the opiate withdrawal syndrome. Nature 371(6493):155\u2013157","journal-title":"Nature"},{"issue":"9","key":"5222_CR36","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1002\/ptr.3736","volume":"26","author":"H Hosseinzadeh","year":"2012","unstructured":"Hosseinzadeh H, Imenshahidi M, Hosseini M, Razavi BM (2012) Effect of linalool on morphine tolerance and dependence in mice. Phytother Res 26(9):1399\u20131404","journal-title":"Phytother Res"},{"issue":"10","key":"5222_CR37","doi-asserted-by":"publisher","first-page":"2494","DOI":"10.1038\/sj.npp.1301634","volume":"33","author":"SL Ingram","year":"2008","unstructured":"Ingram SL, Macey TA, Fossum EN, Morgan MM (2008) Tolerance to repeated morphine administration is associated with increased potency of opioid agonists. Neuropsychopharmacology 33(10):2494\u20132504","journal-title":"Neuropsychopharmacology"},{"issue":"4","key":"5222_CR38","doi-asserted-by":"publisher","first-page":"2836","DOI":"10.1016\/S0021-9258(18)53849-7","volume":"268","author":"T Ishii","year":"1993","unstructured":"Ishii T, Moriyoshi K, Sugihara H, Sakurada K, Kadotani H, Yokoi M et al (1993) Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits. J Biol Chem 268(4):2836\u20132843","journal-title":"J Biol Chem"},{"issue":"2","key":"5222_CR39","first-page":"37","volume":"17","author":"M Kazemi","year":"2021","unstructured":"Kazemi M, Ardjmand A, Shahaboddin ME, Mehrand M, Banitaba-Bidgolia SM, Ghavipanjeh G (2021) Effects of hydroalcoholic extract of Matricaria recutita L. on lipid peroxidation and nitric oxide in pentylenetetrazole-kindled mice: ameliorative effects of hydroalcoholic extract of Matricaria recutita L. on epilepsy. Iran J Pharm Sci 17(2):37\u201350","journal-title":"Iran J Pharm Sci"},{"issue":"6","key":"5222_CR40","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/j.biopsych.2006.02.033","volume":"60","author":"JP Kesby","year":"2006","unstructured":"Kesby JP, Burne THJ, McGrath JJ, Eyles DW (2006) Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: an animal model of schizophrenia. Biol Psychiatry 60(6):591\u2013596","journal-title":"Biol Psychiatry"},{"issue":"2","key":"5222_CR41","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.pbb.2009.04.013","volume":"93","author":"DJ Kim","year":"2009","unstructured":"Kim DJ, King JA, Zuccarelli L, Ferris CF, Koppel GA, Snowdon CT et al (2009) Clavulanic acid: a competitive inhibitor of beta-lactamases with novel anxiolytic-like activity and minimal side effects. Pharmacol Biochem Behav 93(2):112\u2013120","journal-title":"Pharmacol Biochem Behav"},{"issue":"1\u20133","key":"5222_CR42","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1016\/j.ejphar.2008.02.035","volume":"586","author":"G Klein","year":"2008","unstructured":"Klein G, Juni A, Arout CA, Waxman AR, Inturrisi CE, Kest B (2008) Acute and chronic heroin dependence in mice: contribution of opioid and excitatory amino acid receptors. Eur J Pharmacol 586(1\u20133):179\u2013188","journal-title":"Eur J Pharmacol"},{"key":"5222_CR43","doi-asserted-by":"crossref","unstructured":"Koob GF, Volkow ND (2016) Neurobiology of addiction: a neurocircuitry analysis.\u00a0Lancet\u00a0Psych\u00a03(8):760\u2013773. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/27475769","DOI":"10.1016\/S2215-0366(16)00104-8"},{"issue":"2","key":"5222_CR44","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1038\/nrd1958","volume":"5","author":"SA Lipton","year":"2006","unstructured":"Lipton SA (2006) Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond. Nat Rev Drug Discov 5(2):160\u2013170","journal-title":"Nat Rev Drug Discov"},{"issue":"6","key":"5222_CR45","doi-asserted-by":"publisher","first-page":"467","DOI":"10.1007\/s11920-007-0063-1","volume":"9","author":"S Maeng","year":"2007","unstructured":"Maeng S, Zarate JCA (2007) The role of glutamate in mood disorders: results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects. Curr Psychiatry Rep 9(6):467\u2013474","journal-title":"Curr Psychiatry Rep"},{"issue":"8","key":"5222_CR46","doi-asserted-by":"publisher","first-page":"1187","DOI":"10.1016\/j.pnpbp.2003.09.013","volume":"27","author":"E Majercsik","year":"2003","unstructured":"Majercsik E, Haller J, Leveleki C, Baranyi J, Hal\u00e1sz J, Rodgers RJ (2003) The effect of social factors on the anxiolytic efficacy of buspirone in male rats, male mice, and men. Prog Neuropsychopharmacol Biol Psychiatry 27(8):1187\u20131199","journal-title":"Prog Neuropsychopharmacol Biol Psychiatry"},{"issue":"1","key":"5222_CR47","first-page":"53","volume":"27","author":"A Mechri","year":"2001","unstructured":"Mechri A, Saoud M, Khiari G, d\u2019Amato T, Dalery J, Gaha L (2001) Glutaminergic hypothesis of schizophrenia: clinical research studies with ketamine. Encephale 27(1):53\u201359","journal-title":"Encephale"},{"key":"5222_CR48","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1007\/s00213-007-0984-8","volume":"196","author":"IA Mendez","year":"2008","unstructured":"Mendez IA, Trujillo KA (2008) NMDA receptor antagonists inhibit opiate antinociceptive tolerance and locomotor sensitization in rats. Psychopharmacology 196:497\u2013509","journal-title":"Psychopharmacology"},{"issue":"1","key":"5222_CR49","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/S0896-6273(00)81154-X","volume":"26","author":"CJ Messer","year":"2000","unstructured":"Messer CJ, Eisch AJ, Carlezon WAJ, Whisler K, Shen L, Wolf DH et al (2000) Role for GDNF in biochemical and behavioral adaptations to drugs of abuse. Neuron 26(1):247\u2013257","journal-title":"Neuron"},{"key":"5222_CR50","unstructured":"Mohebi E, Molavi M, Mohammadzadeh M, Hosseinzadeh H, Amin B (2020) Clavulanic acid improves ethanol withdrawal symptoms in rats. Iran J Basic Med Sci 23(6):730\u2013736. Available from: https:\/\/ijbms.mums.ac.ir\/article_15478.html"},{"issue":"8","key":"5222_CR51","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1097\/FBP.0b013e3282f18da6","volume":"18","author":"T Mori","year":"2007","unstructured":"Mori T, Ito S, Matsubayashi K, Sawaguchi T (2007) Comparison of nitric oxide synthase inhibitors, phospholipase A2 inhibitor and free radical scavengers as attenuators of opioid withdrawal syndrome. Behav Pharmacol 18(8):725\u2013729","journal-title":"Behav Pharmacol"},{"issue":"5335","key":"5222_CR52","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1126\/science.278.5335.58","volume":"278","author":"EJ Nestler","year":"1997","unstructured":"Nestler EJ, Aghajanian GK (1997) Molecular and cellular basis of addiction. Science 278(5335):58\u201363","journal-title":"Science"},{"issue":"2","key":"5222_CR53","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1139\/Y10-109","volume":"89","author":"E Ozdemir","year":"2011","unstructured":"Ozdemir E, Bagcivan I, Durmus N, Altun A, Gursoy S (2011) The nitric oxide\u2013cGMP signaling pathway plays a significant role in tolerance to the analgesic effect of morphine. Can J Physiol Pharmacol 89(2):89\u201395","journal-title":"Can J Physiol Pharmacol"},{"issue":"2","key":"5222_CR54","doi-asserted-by":"publisher","first-page":"119","DOI":"10.17305\/bjbms.2013.2394","volume":"13","author":"E Ozdemir","year":"2013","unstructured":"Ozdemir E, Bagcivan I, Gursoy S (2013) Role of D1\/D2 dopamin receptors antagonist perphenazine in morphine analgesia and tolerance in rats. Bosn J Basic Med Sci 13(2):119","journal-title":"Bosn J Basic Med Sci"},{"issue":"2\u20133","key":"5222_CR55","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/S0014-2999(02)02961-8","volume":"460","author":"\u00dcK \u00d6zdo\u011fan","year":"2003","unstructured":"\u00d6zdo\u011fan \u00dcK, L\u00e4hdesm\u00e4ki J, Scheinin M (2003) Influence of prazosin and clonidine on morphine analgesia, tolerance and withdrawal in mice. Eur J Pharmacol 460(2\u20133):127\u2013134","journal-title":"Eur J Pharmacol"},{"issue":"17","key":"5222_CR56","doi-asserted-by":"publisher","first-page":"1943","DOI":"10.1016\/S0024-3205(03)00100-0","volume":"72","author":"M \u00d6zek","year":"2003","unstructured":"\u00d6zek M, \u00dcresin Y, G\u00fcng\u00f6r M (2003) Comparison of the effects of specific and nonspecific inhibition of nitric oxide synthase on morphine analgesia, tolerance and dependence in mice. Life Sci 72(17):1943\u20131951","journal-title":"Life Sci"},{"issue":"4","key":"5222_CR57","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1038\/npp.2013.231","volume":"39","author":"A Parsegian","year":"2014","unstructured":"Parsegian A, See RE (2014) Dysregulation of dopamine and glutamate release in the prefrontal cortex and nucleus accumbens following methamphetamine self-administration and during reinstatement in rats. Neuropsychopharmacology 39(4):811\u2013822","journal-title":"Neuropsychopharmacology"},{"issue":"6","key":"5222_CR58","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1097\/00019052-199712000-00017","volume":"10","author":"NS Pilotte","year":"1997","unstructured":"Pilotte NS (1997) Neurochemistry of cocaine withdrawal. Curr Opin Neurol 10(6):534\u2013538","journal-title":"Curr Opin Neurol"},{"issue":"5\u20136","key":"5222_CR59","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1097\/FBP.0b013e32833d41b2","volume":"21","author":"KJ Reissner","year":"2010","unstructured":"Reissner KJ, Kalivas PW (2010) Using glutamate homeostasis as a target for treating addictive disorders. Behav Pharmacol 21(5\u20136):514\u2013522","journal-title":"Behav Pharmacol"},{"issue":"6","key":"5222_CR60","doi-asserted-by":"publisher","first-page":"745","DOI":"10.2174\/1871527314666150529144655","volume":"14","author":"DJ Roberts-Wolfe","year":"2015","unstructured":"Roberts-Wolfe DJ, Kalivas PW (2015) Glutamate transporter GLT-1 as a therapeutic target for substance use disorders. CNS Neurol Disord Drug Targets 14(6):745\u2013756","journal-title":"CNS Neurol Disord Drug Targets"},{"issue":"2","key":"5222_CR61","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/npp.2011.155","volume":"37","author":"M Rodr\u00edguez-Mu\u00f1oz","year":"2012","unstructured":"Rodr\u00edguez-Mu\u00f1oz M, S\u00e1nchez-Bl\u00e1zquez P, Vicente-S\u00e1nchez A, Berrocoso E, Garz\u00f3n J (2012) The mu-opioid receptor and the NMDA receptor associate in PAG neurons: implications in pain control. Neuropsychopharmacology 37(2):338\u2013349","journal-title":"Neuropsychopharmacology"},{"key":"5222_CR62","doi-asserted-by":"crossref","unstructured":"Sadat-Shirazi MS, Zarrindast MR, Daneshparvar H, Ziaie A, Fekri M, Abbasnezhad E et al (2018) Alteration of dopamine receptors subtypes in the brain of opioid abusers: a postmortem study in Iran. Neurosci Lett 687:169\u201376. Available from: https:\/\/www.sciencedirect.com\/science\/article\/pii\/S0304394018306475","DOI":"10.1016\/j.neulet.2018.09.043"},{"issue":"2","key":"5222_CR63","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.2877","volume":"13","author":"M Saeedfar","year":"2023","unstructured":"Saeedfar M, Ardjmand A, Alani B, Ghaderi A, Banafshe HR, Shahaboddin ME et al (2023) The effect of vitamin D on morphine preference in rats: possible biochemical and DRD2\u2013GDNF signaling. Brain Behav 13(2):e2877. https:\/\/doi.org\/10.1002\/brb3.2877","journal-title":"Brain Behav"},{"issue":"2","key":"5222_CR64","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s40487-022-00194-4","volume":"10","author":"A Saeedi Sadr","year":"2022","unstructured":"Saeedi Sadr A, Ehteram H, Seyed Hosseini E, Alizadeh Zarei M, Hassani Bafrani H, Haddad Kashani H (2022) The effect of irisin on proliferation, apoptosis, and expression of metastasis markers in prostate cancer cell lines. Oncol Ther 10(2):377\u2013388","journal-title":"Oncol Ther"},{"issue":"6","key":"5222_CR65","doi-asserted-by":"publisher","first-page":"e11278","DOI":"10.1371\/journal.pone.0011278","volume":"5","author":"P Sanchez-Blazquez","year":"2010","unstructured":"Sanchez-Blazquez P, Rodriguez-Munoz M, Garzon J (2010) Mu-opioid receptors transiently activate the Akt-nNOS pathway to produce sustained potentiation of PKC-mediated NMDAR-CaMKII signaling. PLoS ONE 5(6):e11278","journal-title":"PLoS ONE"},{"issue":"1","key":"5222_CR66","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40659-023-00412-x","volume":"56","author":"E Seyed Hosseini","year":"2023","unstructured":"Seyed Hosseini E, Alizadeh Zarei M, Tarrahimofrad H, Zamani J, Haddad Kashani H, Ahmad E et al (2023) Synergistic effects of dendrosomal nanocurcumin and oxaliplatin on oncogenic properties of ovarian cancer cell lines by down-expression of MMPs. Biol Res 56(1):3","journal-title":"Biol Res"},{"issue":"16","key":"5222_CR67","doi-asserted-by":"publisher","first-page":"5649","DOI":"10.1523\/JNEUROSCI.4564-13.2014","volume":"34","author":"H Shen","year":"2014","unstructured":"Shen H, Scofield MD, Boger H, Hensley M, Kalivas PW (2014) Synaptic glutamate spillover due to impaired glutamate uptake mediates heroin relapse. J Neurosci 34(16):5649\u20135657","journal-title":"J Neurosci"},{"key":"5222_CR68","doi-asserted-by":"crossref","unstructured":"Shen J, Hua G, Li C, Liu S, Liu L, Jiao J (2023) Prevalence, incidence, deaths, and disability-adjusted life-years of drug use disorders for 204 countries and territories during the past 30 years. Asian J Psychiatr 86:103677. Available from: https:\/\/www.sciencedirect.com\/science\/article\/pii\/S1876201823002332","DOI":"10.1016\/j.ajp.2023.103677"},{"issue":"2","key":"5222_CR69","doi-asserted-by":"publisher","first-page":"306","DOI":"10.1016\/j.pharmthera.2007.06.011","volume":"116","author":"TS Shippenberg","year":"2007","unstructured":"Shippenberg TS, Zapata A, Chefer VI (2007) Dynorphin and the pathophysiology of drug addiction. Pharmacol Ther 116(2):306\u2013321","journal-title":"Pharmacol Ther"},{"issue":"4","key":"5222_CR70","doi-asserted-by":"publisher","first-page":"232","DOI":"10.5455\/msm.2011.23.232-234","volume":"23","author":"N Simonovska","year":"2011","unstructured":"Simonovska N, Chibishev A, Babulovska A, Pereska Z, Jurukov I, Glasnovic M (2011) Program of the university clinic of toxicology, Skopje, Republic of Macedonia in treatment of drug addiction (buprenorfin treatment protocol). Materia Socio Medica 23(4):232\u2013234","journal-title":"Materia Socio Medica"},{"issue":"4","key":"5222_CR71","doi-asserted-by":"publisher","first-page":"367","DOI":"10.2174\/1570193X113106660031","volume":"10","author":"J Skrabalova","year":"2013","unstructured":"Skrabalova J, Drastichova Z, Novotny J (2013) Morphine as a potential oxidative stress-causing agent. Mini Rev Org Chem 10(4):367\u2013372","journal-title":"Mini Rev Org Chem"},{"issue":"5","key":"5222_CR72","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.brainresbull.2004.09.005","volume":"64","author":"J Tim\u00e1r","year":"2005","unstructured":"Tim\u00e1r J, Gyarmati Z, F\u00fcrst Z (2005) The development of tolerance to locomotor effects of morphine and the effect of various opioid receptor antagonists in rats chronically treated with morphine. Brain Res Bull 64(5):417\u2013424","journal-title":"Brain Res Bull"},{"issue":"2","key":"5222_CR73","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s002130000416","volume":"151","author":"KA Trujillo","year":"2000","unstructured":"Trujillo KA (2000) Are NMDA receptors involved in opiate-induced neural and behavioral plasticity? A review of preclinical studies. Psychopharmacology 151(2):121\u2013141","journal-title":"Psychopharmacology"},{"issue":"9","key":"5222_CR74","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1046\/j.0953-816x.2001.01775.x","volume":"14","author":"LJMJ Vanderschuren","year":"2001","unstructured":"Vanderschuren LJMJ, De Vries TJ, Wardeh G, Hogenboom FACM, Schoffelmeer ANM (2001) A single exposure to morphine induces long\u2010lasting behavioural and neurochemical sensitization in rats. Eur J Neurosci 14(9):1533\u20131538","journal-title":"Eur J Neurosci"},{"issue":"4","key":"5222_CR75","doi-asserted-by":"publisher","first-page":"863","DOI":"10.1007\/s00213-010-2095-1","volume":"214","author":"MMJ Veeneman","year":"2011","unstructured":"Veeneman MMJ, Boleij H, Broekhoven MH, Snoeren EMS, Guitart Masip M, Cousijn J et al (2011) Dissociable roles of mGlu5 and dopamine receptors in the rewarding and sensitizing properties of morphine and cocaine. Psychopharmacology 214(4):863\u2013876","journal-title":"Psychopharmacology"},{"key":"5222_CR76","doi-asserted-by":"crossref","unstructured":"Verma A, Kulkarni SK (1995) Role of D1\/D2 dopamine and N-methyl-d-aspartate (NMDA) receptors in morphine tolerance and dependence in mice. Eur Neuropsychopharmacol 5(2):81\u201387. Available from: https:\/\/www.sciencedirect.com\/science\/article\/pii\/0924977X94001407","DOI":"10.1016\/0924-977X(94)00140-7"},{"issue":"37","key":"5222_CR77","doi-asserted-by":"publisher","first-page":"15037","DOI":"10.1073\/pnas.1010654108","volume":"108","author":"ND Volkow","year":"2011","unstructured":"Volkow ND, Wang GJ, Fowler JS, Tomasi D, Telang F (2011) Addiction: beyond dopamine reward circuitry. Proc Natl Acad Sci U S A 108(37):15037\u201315042","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"5222_CR78","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1046\/j.1471-4159.1996.66020865.x","volume":"66","author":"JK Wang","year":"1996","unstructured":"Wang JK, Thukral V (1996) Presynaptic NMDA receptors display physiological characteristics of homomeric complexes of NR1 subunits that contain the exon 5 insert in the N-terminal domain. J Neurochem 66(2):865\u2013868","journal-title":"J Neurochem"},{"key":"5222_CR79","doi-asserted-by":"crossref","unstructured":"Weiss SM, Wadsworth G, Fletcher A, Dourish CT (1998) Utility of ethological analysis to overcome locomotor confounds in elevated maze models of anxiety. Neurosci Biobehav Rev 23(2):265\u2013271. Available from: https:\/\/www.sciencedirect.com\/science\/article\/pii\/S014976349800027X","DOI":"10.1016\/S0149-7634(98)00027-X"},{"issue":"1","key":"5222_CR80","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1124\/pr.112.005942","volume":"65","author":"JT Williams","year":"2013","unstructured":"Williams JT, Ingram SL, Henderson G, Chavkin C, von Zastrow M, Schulz S et al (2013) Regulation of mu-opioid receptors: desensitization, phosphorylation, internalization, and tolerance. Pharmacol Rev 65(1):223\u2013254","journal-title":"Pharmacol Rev"},{"issue":"5","key":"5222_CR81","doi-asserted-by":"publisher","first-page":"1366","DOI":"10.1007\/s11064-017-2184-1","volume":"42","author":"P Yue","year":"2017","unstructured":"Yue P, Gao L, Wang X, Ding X, Teng J (2017) Intranasal administration of GDNF protects against neural apoptosis in a rat model of Parkinson\u2019s disease through PI3K\/Akt\/GSK3\u03b2 pathway. Neurochem Res 42(5):1366\u20131374. https:\/\/doi.org\/10.1007\/s11064-017-2184-1","journal-title":"Neurochem Res"},{"key":"5222_CR82","doi-asserted-by":"publisher","first-page":"107343","DOI":"10.1016\/j.yebeh.2020.107343","volume":"112","author":"G Zamanian","year":"2020","unstructured":"Zamanian G, Shayan M, Rahimi N, Bahremand T, Shafaroodi H, Ejtemaei-Mehr S et al (2020) Interaction of morphine tolerance with pentylenetetrazole-induced seizure threshold in mice: the role of NMDA-receptor\/NO pathway. Epilepsy Behav 112:107343","journal-title":"Epilepsy Behav"},{"key":"5222_CR83","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.00082","volume":"11","author":"XS Zeng","year":"2020","unstructured":"Zeng XS, Geng WS, Wang ZQ, Jia JJ (2020) Morphine addiction and oxidative stress: the potential effects of thioredoxin-1. Front Pharmacol 11:82","journal-title":"Front Pharmacol"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05222-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-026-05222-y","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05222-y.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T04:02:02Z","timestamp":1784779322000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-026-05222-y"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":83,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["5222"],"URL":"https:\/\/doi.org\/10.1007\/s00210-026-05222-y","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]},"assertion":[{"value":"22 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This study was conducted in accordance with the ethics committee rules of Kashan University of Medical Sciences (IR.KAUMS.AEC.1402.010).","order":1,"name":"Ethics","label":"Ethics approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","label":"Consent for publication","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}