{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T08:09:36Z","timestamp":1773043776619,"version":"3.50.1"},"reference-count":46,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T00:00:00Z","timestamp":1550534400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["30901403"],"award-info":[{"award-number":["30901403"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007219","name":"Natural Science Foundation of shanghai","doi-asserted-by":"publisher","award":["11ZR1449200"],"award-info":[{"award-number":["11ZR1449200"]}],"id":[{"id":"10.13039\/100007219","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2019,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Opioid\u2010primed relapse is a global burden. Although current strategies have improved, optimal therapy is urgently needed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A recombinant adenovirus (Ad\u2010NEP) expressing \u03b2\u2010endorphin (\u03b2\u2010EP) was designed and injected intracerebroventricularly (icv) into the right lateral ventricle in rats. Spatial and temporal \u03b2\u2010EP expression in the lateral ventricle wall, subventricular zone and adjacent choroid plexus and the \u03b2\u2010EP concentration in the cerebrospinal fluid (CSF) were observed during a 21\u2010day period. A morphine priming\u2010induced conditioned place preference (CPP) rat model was established. The \u03b2\u2010EP\u2010ir neuron counts, CSF \u03b2\u2010EP concentration, and CPP score, which were used to evaluate morphine\u2010primed reinstatement following extinction, were recorded 7 days after the icv injection. Additionally, the rats were pretreated with the irreversible \u03bc opioid receptor antagonist \u03b2\u2010funaltrexamine (\u03b2\u2010FNA) and the selective \u03ba opioid receptor antagonist nor\u2010binaltorphimine (nor\u2010BNI) to identify the receptor\u2010dependent mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Both peak \u03b2\u2010EP expression in target neurons and the peak CSF \u03b2\u2010EP concentration occurred 7 to 8 days after Ad\u2010NEP icv injection. The sustainable increase in the CSF \u03b2\u2010EP concentration was correlated with a decrease in the CPP score 7 days after the Ad\u2010NEP icv injection. Furthermore, reinstatement was almost reversed by \u03b2\u2010FNA pretreatment 24\u2009hours before the behavioral test, but nor\u2010BNI had little effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The increasing cerebrospinal fluid \u03b2\u2010endorphin concentrations showed that the therapeutic effect on opioid relapse occurred predominantly through a \u03bc opioid receptor\u2010dependent mechanism. The Ad\u2010NEP adenovirus can be considered an alternative therapy for opioid relapse.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jmv.25415","type":"journal-article","created":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T09:34:25Z","timestamp":1548927265000},"page":"1158-1167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Transgenic increase in the \u03b2\u2010endorphin concentration in cerebrospinal fluid alleviates morphine\u2010primed relapse behavior through the \u03bc opioid receptor in rats"],"prefix":"10.1002","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1839-6894","authenticated-orcid":false,"given":"Yan","family":"He","sequence":"first","affiliation":[{"name":"Department of Anesthesiology &amp; Intensive Care Eastern Hepatobiliary Hospital, Second Military Medical University Shanghai China"},{"name":"Department of Anesthesiology Fuzhou General Hospital of PLA Fuzhou Fujian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yugang","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Shanghai Pulmonary Hospital, Tongji University School of Medicine Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Shen","sequence":"additional","affiliation":[{"name":"Drug and Equipment Section 442 Clinic Department of Fuzhous General Hospital of PLA Ningde Fujian China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feixiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Intensive Care Eastern Hepatobiliary Hospital, Second Military Medical University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuewu","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology 306 Hospital of PLA Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erliang","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Intensive Care Eastern Hepatobiliary Hospital, Second Military Medical University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhangxiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Pain Clinic of First Affiliated Hospital of Kunming Medical University Kunming Yunnan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuming","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Intensive Care Eastern Hepatobiliary Hospital, Second Military Medical University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weifeng","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology &amp; Intensive Care Eastern Hepatobiliary Hospital, Second Military Medical University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,2,19]]},"reference":[{"key":"e_1_2_6_1_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.14234"},{"key":"e_1_2_6_1_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(17)30375-3"},{"key":"e_1_2_6_1_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00134-006-0165-y"},{"issue":"8","key":"e_1_2_6_1_5_1","first-page":"8","article-title":"Is addiction hereditary?","volume":"22","author":"Miller MC","year":"2006","journal-title":"Harv Ment Health Lett"},{"issue":"2","key":"e_1_2_6_1_6_1","first-page":"70","article-title":"[Psychic dependence in drug addiction: a role of the mesocorticolimbic dopaminergic system]","volume":"107","author":"Polunina AG","year":"2007","journal-title":"Zh Nevrol Psikhiatr Im SS Korsakova"},{"issue":"5","key":"e_1_2_6_1_7_1","first-page":"189","article-title":"[The role of CC\u2010chemokine ligand 2 in the development of psychic dependence on methamphetamine]","volume":"50","author":"Saika F","year":"2015","journal-title":"Nihon Arukoru Yakubutsu Igakkai Zasshi"},{"key":"e_1_2_6_1_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jrh.12178"},{"key":"e_1_2_6_1_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11606-016-3799-7"},{"key":"e_1_2_6_1_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/7620860"},{"key":"e_1_2_6_1_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/00952990902933878"},{"key":"e_1_2_6_1_12_1","doi-asserted-by":"publisher","DOI":"10.2174\/157340609787582864"},{"key":"e_1_2_6_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.02.059"},{"key":"e_1_2_6_1_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(91)90836-K"},{"key":"e_1_2_6_1_15_1","doi-asserted-by":"publisher","DOI":"10.1530\/JME-16-0033"},{"key":"e_1_2_6_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.04.032"},{"key":"e_1_2_6_1_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.16.9608"},{"key":"e_1_2_6_1_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.07.063"},{"key":"e_1_2_6_1_19_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.091553"},{"issue":"1","key":"e_1_2_6_1_20_1","first-page":"15","article-title":"[Neurobiology and psychology of addictions]","volume":"61","author":"Beine A","year":"2006","journal-title":"J Pharm Belg"},{"key":"e_1_2_6_1_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-002-1224-x"},{"key":"e_1_2_6_1_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(00)00239-4"},{"key":"e_1_2_6_1_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(98)00060-4"},{"key":"e_1_2_6_1_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0511030103"},{"key":"e_1_2_6_1_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0165-0270(85)90026-3"},{"key":"e_1_2_6_1_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000336346"},{"key":"e_1_2_6_1_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2012.07.036"},{"issue":"1","key":"e_1_2_6_1_28_1","first-page":"255","article-title":"a highly selective kappa\u2010opioid antagonist in analgesic and receptor binding assays","volume":"246","author":"Takemori AE","year":"1988","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_1_29_1","first-page":"30","article-title":"Nor\u2010binaltorphimine: a potent and selective kappa\u2010opioid receptor antagonist with long\u2010lasting activity in vivo","volume":"316","author":"Endoh T","year":"1992","journal-title":"Arch Int Pharmacodyn Ther"},{"key":"e_1_2_6_1_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneumeth.2013.03.013"},{"key":"e_1_2_6_1_31_1","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2008.0090"},{"issue":"6","key":"e_1_2_6_1_32_1","first-page":"560","article-title":"Associated risk factors to non\u2010compliance to methadone maintenance therapy","volume":"67","author":"Ramli M","year":"2012","journal-title":"Med J Malaysia"},{"issue":"2","key":"e_1_2_6_1_33_1","first-page":"287","article-title":"Rate of adherence to and factors associated with methadone maintenance treatment program (Mmtp) compliance among injecting drug use patients in Nepal","volume":"47","author":"Sharma V","year":"2016","journal-title":"Southeast Asian J Trop Med Public Health"},{"key":"e_1_2_6_1_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/00952990.2017.1286500"},{"key":"e_1_2_6_1_35_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858417714226"},{"key":"e_1_2_6_1_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2012.01.027"},{"key":"e_1_2_6_1_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2006.11.003"},{"key":"e_1_2_6_1_38_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.115.229542"},{"key":"e_1_2_6_1_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-009-0602-4"},{"issue":"3","key":"e_1_2_6_1_40_1","first-page":"1006","article-title":"Mu antagonist and kappa agonist properties of beta\u2010funaltrexamine (beta\u2010FNA) in vivo: long\u2010lasting spinal analgesia in mice","volume":"252","author":"Qi JA","year":"1990","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_6_1_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0149877"},{"issue":"2","key":"e_1_2_6_1_42_1","first-page":"151","article-title":"CPP\u2010ACP complex as a new adjunctive agent for remineralisation: a review","volume":"9","author":"Gupta R","year":"2011","journal-title":"Oral Health Prev Dent"},{"key":"e_1_2_6_1_43_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.16m10657"},{"key":"e_1_2_6_1_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2017.04.005"},{"key":"e_1_2_6_1_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-3271-9_31"},{"key":"e_1_2_6_1_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2012.05.008"},{"key":"e_1_2_6_1_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0740-5472(02)00274-X"}],"container-title":["Journal of Medical Virology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjmv.25415","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.25415","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jmv.25415","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jmv.25415","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T09:13:56Z","timestamp":1694337236000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jmv.25415"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,19]]},"references-count":46,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["10.1002\/jmv.25415"],"URL":"https:\/\/doi.org\/10.1002\/jmv.25415","archive":["Portico"],"relation":{},"ISSN":["0146-6615","1096-9071"],"issn-type":[{"value":"0146-6615","type":"print"},{"value":"1096-9071","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,19]]},"assertion":[{"value":"2018-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-11-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-19","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}