{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:51:19Z","timestamp":1784631079471,"version":"3.55.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,5,23]],"date-time":"2024-05-23T00:00:00Z","timestamp":1716422400000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81801320"],"award-info":[{"award-number":["81801320"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LY22H090015"],"award-info":[{"award-number":["LY22H090015"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017594","name":"Medical Science and Technology Project of Zhejiang Province","doi-asserted-by":"publisher","award":["2022RC050"],"award-info":[{"award-number":["2022RC050"]}],"id":[{"id":"10.13039\/501100017594","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Addiction Biology"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Addictive properties of propofol have been demonstrated in both humans and animals. The nucleus accumbens (NAc) shell (NAsh) in the brain, along with the interactions between N\u2010methyl\u2010D\u2010aspartate receptor (NMDAR) and the dopamine D1 receptor (D1R), as well as their downstream ERK\/CREB signalling pathway in the NAc, are integral in regulating reward\u2010seeking behaviour. Nevertheless, it remains unclear whether NMDARs and the NMDAR\u2010D1R\/ERK\/CREB signalling pathway in the NAsh are involved in mediating propofol addiction. To investigate it, we conducted experiments with adult male Sprague\u2013Dawley rats to establish a model of propofol self\u2010administration behaviour. Subsequently, we microinjected D\u2010AP5 (a competitive antagonist of NMDARs, 1.0\u20134.0\u00a0\u03bcg\/0.3\u00a0\u03bcL\/site) or vehicle into bilateral NAsh in rats that had previously self\u2010administered propofol to examine the impact of NMDARs within the NAsh on propofol self\u2010administration behaviour. Additionally, we examined the protein expressions of NR2A and NR2B subunits, and the D1R\/ERK\/CREB signalling pathways within the NAc. The results revealed that propofol administration behaviour was enhanced by D\u2010AP5 pretreatment in NAsh, accompanied by elevated expressions of phosphorylation of NR2A (Tyr1246) and NR2B (Tyr1472) subunits. There were statistically significant increases in the expressions of D1Rs, as well as in the phosphorylated ERK1\/2 (p\u2010ERK1\/2) and CREB (p\u2010CREB). This evidence substantiates a pivotal role of NMDARs in the NAsh, with a particular emphasis on the NR2A and NR2B subunits, in mediating propofol self\u2010administration behaviour. Furthermore, it suggests that this central reward processing mechanism may operate through the NMDAR\u2010D1R\/ERK\/CREB signal transduction pathway.<\/jats:p>","DOI":"10.1111\/adb.13401","type":"journal-article","created":{"date-parts":[[2024,5,24]],"date-time":"2024-05-24T01:54:40Z","timestamp":1716515680000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["NMDA receptor within nucleus accumbens shell regulates propofol self\u2010administration through D1R\/ERK\/CREB signalling pathway"],"prefix":"10.1111","volume":"29","author":[{"given":"Jiajia","family":"Li","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingwu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiani","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenchen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Clinical Research Unit The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanglei","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingquan","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7953-0992","authenticated-orcid":false,"given":"Binbin","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Perioperative and Pain Medicine The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Anesthesiology of Zhejiang Province The Second Affiliated Hospital of Wenzhou Medical University  Wenzhou China"},{"name":"Key Laboratory of Pediatric Anesthesiology, Ministry of Education Wenzhou Medical University  Wenzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,5,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/ADM.0b013e3182872901"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yrtph.2015.02.001"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2165\/00044011\u2010200323010\u201000003"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1213\/01.ane.0000270215.86253.30"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.04.029"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0376\u20108716(99)00044\u20107"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.11.002"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.13310"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2009.02.005"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1213\/ANE.0b013e318222af17"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.132472"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1213\/00000539\u2010200210000\u201000022"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0074\u20107742(09)89006\u20105"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028\u20103908(95)00109\u2010J"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2015.11.063"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0896\u20106273(94)90210\u20100"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1329\u201009.2009"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306\u20104522(01)00483\u20103"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2006.02.117"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1101\/lm.035113.114"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.032654599"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21\u201015\u201005546.2001"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12671"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0408305102"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12871\u2010020\u201001056\u20100"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nlm.2017.03.022"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2020.134819"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2008.179"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/syn.21905"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002130000636"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.22\u201007\u201002916.2002"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14290"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091\u20103057(95)00074\u20107"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471\u20104159.1995.64052080.x"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1098\u20102396(199707)26:3<225::AID\u2010SYN4>3.0.CO;2\u20109"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.15\u201005\u201003896.1995"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(84)90239\u20107"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1220591110"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2014.00066"},{"issue":"1","key":"e_1_2_8_41_1","first-page":"13","article-title":"Role of tyrosine kinase\u2010dependent phosphorylation of NR2B subunit\u2010containing NMDA receptor in morphine reward","volume":"42","author":"Kato H","year":"2007","journal-title":"Nihon Arukoru Yakubutsu Igakkai Zasshi"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1124\/mol.65.1.121"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn912"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2012.06.012"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2009.11"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyv030"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3070\u201011.2011"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/dta.1987"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12640-011-9250-2"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006\u20108993(94)91977\u20101"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.04.031"}],"container-title":["Addiction Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/adb.13401","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,29]],"date-time":"2024-11-29T15:32:15Z","timestamp":1732894335000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/adb.13401"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2024,5]]}},"alternative-id":["10.1111\/adb.13401"],"URL":"https:\/\/doi.org\/10.1111\/adb.13401","archive":["Portico"],"relation":{},"ISSN":["1355-6215","1369-1600"],"issn-type":[{"value":"1355-6215","type":"print"},{"value":"1369-1600","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5]]},"assertion":[{"value":"2023-10-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-04-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-05-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13401"}}