{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T11:15:48Z","timestamp":1793531748383,"version":"4.5.0"},"reference-count":55,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/100019803","name":"Center for Health Sciences, Oklahoma State University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019803","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Biochemistry and Behavior"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.pbb.2025.174052","type":"journal-article","created":{"date-parts":[[2025,6,10]],"date-time":"2025-06-10T02:44:39Z","timestamp":1749523479000},"page":"174052","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"special_numbering":"C","title":["Xylazine co-administration influences the rewarding properties of heroin and withdrawal in male rats"],"prefix":"10.1016","volume":"254","author":[{"given":"Mason","family":"Hochstetler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Dodge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Songjukta","family":"Chakraborty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Jeffers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swarup","family":"Mitra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"2","key":"10.1016\/j.pbb.2025.174052_bb0005","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1080\/17425255.2020.1721458","article-title":"Pharmacokinetic and pharmacodynamic considerations in developing a response to the opioid epidemic","volume":"16","author":"Balyan","year":"2020","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"10.1016\/j.pbb.2025.174052_bb0010","doi-asserted-by":"crossref","first-page":"100155","DOI":"10.1016\/j.addicn.2024.100155","article-title":"Xylazine is an agonist at kappa opioid receptors and exhibits sex-specific responses to opioid antagonism","volume":"11","author":"Bedard","year":"2024","journal-title":"Addiction Neuroscience"},{"issue":"2","key":"10.1016\/j.pbb.2025.174052_bb0015","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1016\/j.jaad.2023.04.009","article-title":"Skin ulcerations caused by xylazine: A lesser-known entity","volume":"89","author":"Bishnoi","year":"2023","journal-title":"J. Am. Acad. Dermatol."},{"issue":"1","key":"10.1016\/j.pbb.2025.174052_bb0020","doi-asserted-by":"crossref","DOI":"10.1186\/s12954-021-00546-9","article-title":"Xylazine detected in unregulated opioids and drug administration equipment in Toronto, Canada: clinical and social implications","volume":"18","author":"Bowles","year":"2021","journal-title":"Harm Reduct. J."},{"key":"10.1016\/j.pbb.2025.174052_bb0025","doi-asserted-by":"crossref","DOI":"10.1016\/j.drugalcdep.2024.112450","article-title":"Effects of xylazine on naloxone-precipitated fentanyl withdrawal in male and female rats","volume":"264","author":"Carlson","year":"2024","journal-title":"Drug Alcohol Depend."},{"key":"10.1016\/j.pbb.2025.174052_bb0030","author":"CDC"},{"key":"10.1016\/j.pbb.2025.174052_bb0035","author":"CDC"},{"key":"10.1016\/j.pbb.2025.174052_bb0040","author":"CDC"},{"issue":"7","key":"10.1016\/j.pbb.2025.174052_bb0045","doi-asserted-by":"crossref","first-page":"1561","DOI":"10.1007\/s00213-023-06390-y","article-title":"Xylazine effects on opioid-induced brain hypoxia","volume":"240","author":"Choi","year":"2023","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.pbb.2025.174052_bb0050","series-title":"The undervalued issue of drug of abuse adulterants' toxicity: the Italian perspective","author":"Ciancio","year":"2024"},{"issue":"7","key":"10.1016\/j.pbb.2025.174052_bb0055","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1111\/add.16466","article-title":"Broad evidence of xylazine in the UK illicit drug market beyond heroin supplies: triangulating from toxicology, drug-testing and law enforcement","volume":"119","author":"Copeland","year":"2024","journal-title":"Addiction"},{"issue":"1","key":"10.1016\/j.pbb.2025.174052_bb0060","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0376-8716(84)90014-0","article-title":"Adulterants in heroin\/cocaine: implications concerning heroin-associated nephropathy","volume":"14","author":"Cunningham","year":"1984","journal-title":"Drug Alcohol Depend."},{"issue":"23","key":"10.1016\/j.pbb.2025.174052_bb0065","doi-asserted-by":"crossref","first-page":"14619","DOI":"10.3390\/ijms232314619","article-title":"Molecular insights and clinical outcomes of drugs of abuse adulteration: new trends and new psychoactive substances","volume":"23","author":"Di Trana","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.pbb.2025.174052_bb0070","doi-asserted-by":"crossref","first-page":"119826","DOI":"10.1016\/j.cca.2024.119826","article-title":"\u201cTranq-dope\u201d: the first fatal intoxication due to xylazine-adulterated heroin in Italy","volume":"561","author":"Di Trana","year":"2024","journal-title":"Clin. Chim. Acta"},{"issue":"10","key":"10.1016\/j.pbb.2025.174052_bb0075","doi-asserted-by":"crossref","first-page":"1370","DOI":"10.7326\/M23-2001","article-title":"Xylazine adulteration of the heroin\u2013fentanyl drug supply","volume":"176","author":"D'Orazio","year":"2023","journal-title":"Ann. Intern. Med."},{"key":"10.1016\/j.pbb.2025.174052_bb0080","series-title":"January 17","author":"Dydyk","year":"2024"},{"issue":"5","key":"10.1016\/j.pbb.2025.174052_bb0085","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1007\/s11916-024-01211-z","article-title":"Xylazine: a drug adulterant of clinical concern","volume":"28","author":"Edinoff","year":"2024","journal-title":"Curr. Pain Headache Rep."},{"issue":"5","key":"10.1016\/j.pbb.2025.174052_bb0090","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1097\/ADM.0000000000000955","article-title":"Management of Xylazine Withdrawal in a hospitalized patient: A case report","volume":"16","author":"Ehrman-Dupre","year":"2022","journal-title":"J. Addict. Med."},{"issue":"3","key":"10.1016\/j.pbb.2025.174052_bb0095","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1097\/00063110-200309000-00022","article-title":"Drug abuse with inhalated xylazine","volume":"10","author":"Elejalde","year":"2003","journal-title":"Eur J Emerg Med"},{"key":"10.1016\/j.pbb.2025.174052_bb0100","doi-asserted-by":"crossref","first-page":"109380","DOI":"10.1016\/j.drugalcdep.2022.109380","article-title":"Xylazine spreads across the US: A growing component of the increasingly synthetic and polysubstance overdose crisis","volume":"233","author":"Friedman","year":"2022","journal-title":"Drug Alcohol Depend."},{"issue":"10","key":"10.1016\/j.pbb.2025.174052_bb0105","doi-asserted-by":"crossref","first-page":"1776","DOI":"10.1038\/s41386-022-01279-4","article-title":"Histone H3 dopaminylation in ventral tegmental area underlies heroin-induced transcriptional and behavioral plasticity in male rats","volume":"47","author":"Fulton","year":"2022","journal-title":"Neuropsychopharmacology"},{"issue":"1","key":"10.1016\/j.pbb.2025.174052_bb0110","doi-asserted-by":"crossref","DOI":"10.1186\/s12889-024-18459-0","article-title":"Adulterants present in the San Diego County fentanyl supply: a laboratory analysis of seized law enforcement samples","volume":"24","author":"Galust","year":"2024","journal-title":"BMC Public Health"},{"issue":"5","key":"10.1016\/j.pbb.2025.174052_bb0115","article-title":"Alpha2-adrenergic agonists for the management of opioid withdrawal. Cochrane","volume":"2016","author":"Gowing","year":"2016","journal-title":"Library"},{"issue":"4","key":"10.1016\/j.pbb.2025.174052_bb0120","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1111\/j.1365-2885.1988.tb00189.x","article-title":"Xylazine \u2013 a review of its pharmacology and use in veterinary medicine","volume":"11","author":"Greene","year":"1988","journal-title":"J. Vet. Pharmacol. Ther."},{"issue":"24","key":"10.1016\/j.pbb.2025.174052_bb0125","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1056\/NEJMp2303120","article-title":"Xylazine \u2014 medical and public health imperatives","volume":"388","author":"Gupta","year":"2023","journal-title":"N. Engl. J. Med."},{"issue":"1","key":"10.1016\/j.pbb.2025.174052_bb0130","doi-asserted-by":"crossref","first-page":"130","DOI":"10.21608\/rpbs.2024.299738.1305","article-title":"Adulterations within illicit drugs: forensic prospection","volume":"8","author":"Heneedak","year":"2024","journal-title":"Records of Pharmaceutical and Biomedical Sciences\/Records of Pharmaceutical & Biomedical Sciences"},{"issue":"4","key":"10.1016\/j.pbb.2025.174052_bb0135","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1093\/jat\/25.4.245","article-title":"Severe intoxication with the veterinary tranquilizer Xylazine in humans","volume":"25","author":"Hoffmann","year":"2001","journal-title":"J. Anal. Toxicol."},{"issue":"1","key":"10.1016\/j.pbb.2025.174052_bb0140","article-title":"Preventing overdoses involving stimulants: the POINTS study protocol","volume":"24","author":"Jaclyn","year":"2024","journal-title":"BMC Public Health"},{"issue":"4","key":"10.1016\/j.pbb.2025.174052_bb0145","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1136\/injuryprev-2020-043968","article-title":"Increasing presence of xylazine in heroin and\/or fentanyl deaths, Philadelphia, Pennsylvania, 2010\u20132019","volume":"27","author":"Johnson","year":"2021","journal-title":"Inj. Prev."},{"issue":"26","key":"10.1016\/j.pbb.2025.174052_bb0150","first-page":"719","article-title":"Vital signs: demographic and substance use trends among heroin users \u2014 United States, 2002\u20132013","volume":"64","author":"Jones","year":"2015","journal-title":"Am. J. Public Health"},{"issue":"2","key":"10.1016\/j.pbb.2025.174052_bb0155","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1037\/pha0000670","article-title":"Xylazine suppresses fentanyl consumption during self-administration and induces a unique sex-specific withdrawal syndrome that is not altered by naloxone in rats","volume":"32","author":"Khatri","year":"2024","journal-title":"Exp. Clin. Psychopharmacol."},{"issue":"14","key":"10.1016\/j.pbb.2025.174052_bb0160","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1001\/jama.2013.278861","article-title":"SAMHSA: pain medication abuse a common path to heroin","volume":"310","author":"Kuehn","year":"2013","journal-title":"JAMA"},{"issue":"3","key":"10.1016\/j.pbb.2025.174052_bb0165","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.pbb.2008.03.018","article-title":"Heroin self-administration: I. Incubation of goal-directed behavior in rats","volume":"90","author":"Kuntz","year":"2008","journal-title":"Pharmacol. Biochem. Behav."},{"issue":"3","key":"10.1016\/j.pbb.2025.174052_bb0170","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.pbb.2008.03.019","article-title":"Heroin self-administration: II. CNS gene expression following withdrawal and cue-induced drug-seeking behavior","volume":"90","author":"Kuntz","year":"2008","journal-title":"Pharmacol. Biochem. Behav."},{"key":"10.1016\/j.pbb.2025.174052_bb0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuint.2024.105785","article-title":"Novel psychoplastogen DM506 reduces cue-induced heroin-seeking and inhibits tonic GABA currents in the Prelimbic cortex","volume":"178","author":"Looschen","year":"2024","journal-title":"Neurochem. Int."},{"key":"10.1016\/j.pbb.2025.174052_bb0180","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/00952990.2025.2469793","article-title":"Adolescent stress avoidance influences cue-induced heroin seeking and chaperonin gene expression in the dorsal striatum of adult female rats","author":"Looschen","year":"2025","journal-title":"Am. J. Drug Alcohol Abuse"},{"issue":"3","key":"10.1016\/j.pbb.2025.174052_bb0185","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1080\/15563650.2022.2159427","article-title":"Opioid overdoses involving xylazine in emergency department patients: a multicenter study","volume":"61","author":"Love","year":"2023","journal-title":"Clin. Toxicol."},{"issue":"5","key":"10.1016\/j.pbb.2025.174052_bb0190","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1001\/jamapsychiatry.2017.0163","article-title":"The surge of opioid use, addiction, and overdoses","volume":"74","author":"Madras","year":"2017","journal-title":"JAMA Psychiatr."},{"issue":"11","key":"10.1016\/j.pbb.2025.174052_bb0195","doi-asserted-by":"crossref","first-page":"3539","DOI":"10.1007\/s00213-022-06226-1","article-title":"EGR3 regulates opioid-related nociception and motivation in male rats","volume":"239","author":"Mitra","year":"2022","journal-title":"Psychopharmacology"},{"issue":"6","key":"10.1016\/j.pbb.2025.174052_bb0200","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.biopsych.2024.06.028","article-title":"A novel role for the histone demethylase JMJD3 in mediating heroin-induced relapse-like behaviors","volume":"97","author":"Mitra","year":"2025","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.pbb.2025.174052_bb0205","doi-asserted-by":"crossref","first-page":"104154","DOI":"10.1016\/j.drugpo.2023.104154","article-title":"Xylazine in the drug supply: emerging threats and lessons learned in areas with high levels of adulteration","volume":"120","author":"Quijano","year":"2023","journal-title":"Int. J. Drug Policy"},{"key":"10.1016\/j.pbb.2025.174052_bb0210","doi-asserted-by":"crossref","DOI":"10.1016\/j.dadr.2022.100074","article-title":"Perspectives of people in Philadelphia who use fentanyl\/heroin adulterated with the animal tranquilizer xylazine; making a case for xylazine test strips","volume":"4","author":"Reed","year":"2022","journal-title":"Drug and Alcohol Dependence Reports"},{"issue":"10","key":"10.1016\/j.pbb.2025.174052_bb2210","doi-asserted-by":"crossref","first-page":"2600","DOI":"10.1111\/add.15458","article-title":"Heroin use cannot be measured adequately with a general population survey","volume":"116","author":"Reuter","year":"2021","journal-title":"Addiction"},{"issue":"2","key":"10.1016\/j.pbb.2025.174052_bb0215","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s00213-019-05373-2","article-title":"Acute naloxone-precipitated morphine withdrawal elicits nausea-like somatic behaviors in rats in a manner suppressed by N-oleoylglycine","volume":"237","author":"Rock","year":"2019","journal-title":"Psychopharmacology"},{"issue":"1\u20132","key":"10.1016\/j.pbb.2025.174052_bb0220","first-page":"3","article-title":"The reinstatement model of drug relapse: history, methodology and major findings","volume":"168","author":"Shaham","year":"2002","journal-title":"Psychopharmacology"},{"issue":"1","key":"10.1016\/j.pbb.2025.174052_bb0225","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1177\/0033354919887741","article-title":"The emerging role of toxic adulterants in street drugs in the US illicit opioid crisis","volume":"135","author":"Singh","year":"2019","journal-title":"Public Health Rep."},{"issue":"7","key":"10.1016\/j.pbb.2025.174052_bb0230","doi-asserted-by":"crossref","DOI":"10.2174\/1389201018666170710184531","article-title":"Adulteration practices of psychoactive illicit drugs: an updated review","volume":"18","author":"Solimini","year":"2017","journal-title":"Curr. Pharm. Biotechnol."},{"key":"10.1016\/j.pbb.2025.174052_bb0235","doi-asserted-by":"crossref","DOI":"10.1016\/j.drugalcdep.2024.111282","article-title":"Xylazine does not enhance fentanyl reinforcement in rats: a behavioral economic analysis","volume":"258","author":"St. Onge","year":"2024","journal-title":"Drug Alcohol Depend."},{"issue":"1","key":"10.1016\/j.pbb.2025.174052_bb0240","doi-asserted-by":"crossref","DOI":"10.1038\/s41572-019-0137-5","article-title":"Opioid use disorder","volume":"6","author":"Strang","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"issue":"4","key":"10.1016\/j.pbb.2025.174052_bb0245","doi-asserted-by":"crossref","first-page":"S29","DOI":"10.1016\/j.annemergmed.2021.09.080","article-title":"71 adulteration of illicit drugs in emergency department patients with acute opioid overdose: A multicenter cohort","volume":"78","author":"Study","year":"2021","journal-title":"Ann. Emerg. Med."},{"key":"10.1016\/j.pbb.2025.174052_bb0250","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1007\/s00213-012-2784-z","article-title":"Association of time-dependent changes in mu opioid receptor mRNA, but not BDNF, TrkB, or MeCP2 mRNA and protein expression in the rat nucleus accumbens with incubation of heroin craving","volume":"224","author":"Theberge","year":"2012","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.pbb.2025.174052_bb0255","doi-asserted-by":"crossref","DOI":"10.1177\/26331055241247156","article-title":"Collateral damage: neurological correlates of non-fatal overdose in the era of fentanyl-xylazine","volume":"19","author":"Todaro","year":"2024","journal-title":"Neurosci. Insights"},{"issue":"1","key":"10.1016\/j.pbb.2025.174052_bb0260","doi-asserted-by":"crossref","DOI":"10.1186\/1747-597X-6-7","article-title":"Xylazine (veterinary sedative) use in Puerto Rico","volume":"6","author":"Torruella","year":"2011","journal-title":"Substance Abuse Treatment Prevention and Policy"},{"issue":"22","key":"10.1016\/j.pbb.2025.174052_bb0265","doi-asserted-by":"crossref","DOI":"10.1172\/JCI183354","article-title":"Xylazine induces dopamine release and augments the effects of fentanyl","volume":"134","author":"Trinko","year":"2024","journal-title":"J. Clin. Invest."},{"issue":"1","key":"10.1016\/j.pbb.2025.174052_bb0270","article-title":"Reducing the harms of xylazine: clinical approaches, research deficits, and public health context","volume":"20","author":"Zagorski","year":"2023","journal-title":"Harm Reduct. J."}],"container-title":["Pharmacology Biochemistry and Behavior"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091305725000991?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0091305725000991?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:45:43Z","timestamp":1776919543000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0091305725000991"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":55,"alternative-id":["S0091305725000991"],"URL":"https:\/\/doi.org\/10.1016\/j.pbb.2025.174052","relation":{},"ISSN":["0091-3057"],"issn-type":[{"value":"0091-3057","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Xylazine co-administration influences the rewarding properties of heroin and withdrawal in male rats","name":"articletitle","label":"Article Title"},{"value":"Pharmacology Biochemistry and Behavior","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.pbb.2025.174052","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"174052"}}