{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T15:10:50Z","timestamp":1774278650182,"version":"3.50.1"},"reference-count":65,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2023,2,13]],"date-time":"2023-02-13T00:00:00Z","timestamp":1676246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81872930"],"award-info":[{"award-number":["81872930"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073922"],"award-info":[{"award-number":["82073922"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173884"],"award-info":[{"award-number":["82173884"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012176","name":"Project 211","doi-asserted-by":"publisher","award":["CPU2018GY22"],"award-info":[{"award-number":["CPU2018GY22"]}],"id":[{"id":"10.13039\/501100012176","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Liver failure is associated with psychiatric alterations, partly resulting from the increased brain dopamine levels. We investigated the relationship between increased dopamine levels and mental abnormalities using bile duct ligation (BDL) rats and the mechanism by which liver failure increased dopamine levels in SH\u2010SY5Y cells.<\/jats:p><jats:p>Behavioural tests were carried out on day 13 and 27 following BDL, along with measurements of dopamine and metabolites, expressions of enzymes and transporters related to dopamine metabolism, and its transport into the cortex and the hippocampus. SH\u2010SY5Y cells were used to investigate whether NH<jats:sub>4<\/jats:sub>Cl, bile acids and bilirubin affected expression of tyrosine hydroxylase or not. Tyrosine hydroxylase (TH) expression in SH\u2010SY5Y cells co\u2010incubated with bilirubin and signal pathway inhibitors was measured.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Open\u2010field test results demonstrated BDL rats showed anxiety\u2010like behaviour, accompanied by increased dopamine levels and expression of TH protein in the cortex. Membrane bound long form (MB)\u2010COMT, slightly but significantly decreased. SH\u2010SY5Y cells indicated that increased bilirubin levels was a factor in inducing TH expression. Both inhibitor of NF\u2010\u03baB pathway BAY 11\u20107082 and silencing NF\u2010\u03baB p65 reversed bilirubin\u2010induced upregulation of TH protein. NF\u2010\u03baB activator TNF\u2010\u03b1 increased expression of TH protein. Roles of bilirubin in increases of TH protein expressions and dopamine levels were measured using hyperbilirubinemia rats. Anxiety\u2010like behaviour, was associated with increased dopamine levels and TH protein expressions in hyperbilirubinemia rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>BDL significantly increased dopamine levels in rat cortex partly due to bilirubin\u2010mediated TH induction. Increased bilirubin induced TH expression via activating NF\u2010\u03baB signalling pathway.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.16041","type":"journal-article","created":{"date-parts":[[2023,1,24]],"date-time":"2023-01-24T15:10:51Z","timestamp":1674573051000},"page":"1690-1709","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Bile duct ligation increased dopamine levels in the cerebral cortex of rats partly due to induction of tyrosine hydroxylase"],"prefix":"10.1111","volume":"180","author":[{"given":"Weimin","family":"Kong","sequence":"first","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy China Pharmaceutical University  Nanjing China"},{"name":"School of Pharmacy Bengbu Medical College  2600 Donghai Road Bengbu Anhui China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7215-555X","authenticated-orcid":false,"given":"Xueying","family":"Sun","sequence":"additional","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siyu","family":"Yu","sequence":"additional","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4512-570X","authenticated-orcid":false,"given":"Peihua","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoke","family":"Zheng","sequence":"additional","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Hunan Provincial People's Hospital (The first\u2010affiliated hospital of Hunan Normal University)  Changsha China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianxin","family":"Jiang","sequence":"additional","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengmeng","family":"Jin","sequence":"additional","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinghui","family":"Gao","sequence":"additional","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomin","family":"Fan","sequence":"additional","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8476-2007","authenticated-orcid":false,"given":"Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Drug Metabolism and Pharmacokinetics, School of Pharmacy China Pharmaceutical University  Nanjing China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,2,13]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15538"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510x(82)90040-5"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6826175"},{"issue":"2","key":"e_1_2_12_6_1","first-page":"1691","article-title":"Oral administration of oleanolic acid, isolated from Swertia mussotii Franch, attenuates liver injury, inflammation, and cholestasis in bile duct\u2010ligated rats","volume":"8","author":"Chai J.","year":"2015","journal-title":"International Journal of Clinical and Experimental Medicine"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp070032u"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0165-0270(00)00205-3"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.21.7.565"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2015.01.042"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000366391"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2014.2386"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-013-9431-6"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-015-9445-2"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2017.09.040"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1037\/bul0000096"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1039856219875054"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acthis.2013.01.006"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tox.2017.12.003"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/gastro\/gox013"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161209789058165"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2006.03680.x"},{"issue":"4","key":"e_1_2_12_24_1","first-page":"413","article-title":"Long\u2010term portocaval shunt and changes in rat brain amine systems","volume":"7","author":"Fogel W. A.","year":"1999","journal-title":"Neurobiology (Budapest, Hungary)"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2018.07.008"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000506052"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.65031166.x"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2016.06.020"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpim.59"},{"key":"e_1_2_12_30_1","first-page":"103","article-title":"Brain monoamines in hepatic encephalopathy and other types of metabolic coma","volume":"14","author":"Jellinger K.","year":"1978","journal-title":"Journal of Neural Transmission"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000001010"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2015.07.125"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/734703"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-62703-640-5_2"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-8994-2_9"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/BPH.15178"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-13-7647-4_3"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.203"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2020.461032"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1997.68031200.x"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-012-9364-0"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2016.04.009"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.07.025"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2016.07.011"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00160.2007"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2013.11.010"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1159\/000356422"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1159\/000065949"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-013-9465-9"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1006896111280"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(93)90126-8"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2013.01.023"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v11.i35.5444"},{"key":"e_1_2_12_55_1","doi-asserted-by":"publisher","DOI":"10.3233\/RNN-170728"},{"key":"e_1_2_12_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02774854"},{"key":"e_1_2_12_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-3057(82)90507-x"},{"key":"e_1_2_12_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3644"},{"key":"e_1_2_12_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep44154"},{"key":"e_1_2_12_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2016.01.007"},{"key":"e_1_2_12_61_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-018-1018-z"},{"key":"e_1_2_12_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-020-00602-3"},{"key":"e_1_2_12_63_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2016.25"},{"key":"e_1_2_12_64_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840120413"},{"key":"e_1_2_12_65_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2019.01433"},{"key":"e_1_2_12_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2019.04.056"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.16041","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bph.16041","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.16041","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T12:28:19Z","timestamp":1692448099000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.16041"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,2,13]]},"references-count":65,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["10.1111\/bph.16041"],"URL":"https:\/\/doi.org\/10.1111\/bph.16041","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,2,13]]},"assertion":[{"value":"2021-02-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-18","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-02-13","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}