{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T22:58:46Z","timestamp":1776898726996,"version":"3.51.2"},"reference-count":59,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071496 to Rao Fu"],"award-info":[{"award-number":["82071496 to Rao Fu"]}],"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":["82571703 to Rao Fu"],"award-info":[{"award-number":["82571703 to Rao Fu"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2024A1515013166 to Rao Fu"],"award-info":[{"award-number":["2024A1515013166 to Rao Fu"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100017610","name":"Shenzhen Science and Technology Innovation Program","doi-asserted-by":"publisher","award":["JCYJ20220530145401003 to Rao Fu"],"award-info":[{"award-number":["JCYJ20220530145401003 to Rao Fu"]}],"id":[{"id":"10.13039\/501100017610","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alcohol use disorder (AUD) is a chronic condition marked by compulsive drinking and withdrawal\u2010related negative affect. Histamine (HA) signaling, particularly via the histamine H3 receptor (H3R), may modulate alcohol\u2010related behaviors. We investigated the effects of pitolisant, an FDA\u2010approved H3R antagonist, on ethanol (EtOH)\u2010related behaviors in mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Adult male C57BL\/6J mice underwent acute or chronic (2 or &gt;\u20098\u2009weeks) intermittent alcohol exposure. Pitolisant pretreatment was administered, and then pharmacological behavior, histologic, and molecular assays were conducted.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Result<\/jats:title>\n                    <jats:p>Pitolisant administration reduced acute EtOH\u2010induced locomotor activation, conditioned place preference, and sedative effects, and also curtailed EtOH intake. It alleviated anxiety and depression\u2010like behavior during 24\u2010h withdrawal (Post\u2010EtOH). Mechanistically, the Post\u2010EtOH condition was featured by complicated brain cFos expression mapping, including elevated cFos, [HA] and [glutamine]\/[glutamate] ratio in the lateral habenula (LHb). However, systemic pitolisant treatment significantly increased [norepinephrine]\/[normetanephrine] ratio, and restored the diminished phosphorylated CREB and BDNF levels in the LHb. Intra\u2010LHb H2R antagonist cimetidine infusion partly blocked the pitolisant therapeutic effect on alcohol\u2010related behavior.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings highlight the HAergic system as a critical regulator of alcohol\u2010related behaviors. The LHb HA signaling and norepinephrine neurotransmission might underlie pitolisant's potential novel therapeutic strategy for AUD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70732","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T09:17:51Z","timestamp":1767691071000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pitolisant Inhibits Alcohol Drinking and Improves Withdrawal Negative Affect Through Lateral Habenula Histaminergic Signaling in Mice"],"prefix":"10.1002","volume":"32","author":[{"given":"Yan","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pharmacology Naval Medical University\/Second Military Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yixin","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine Shenzhen Campus of Sun Yat\u2010Sen University, Sun Yat\u2010Sen University  Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianhao","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine Shenzhen Campus of Sun Yat\u2010Sen University, Sun Yat\u2010Sen University  Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zanhao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine Shenzhen Campus of Sun Yat\u2010Sen University, Sun Yat\u2010Sen University  Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengzhong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine Shenzhen Campus of Sun Yat\u2010Sen University, Sun Yat\u2010Sen University  Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine Shenzhen Campus of Sun Yat\u2010Sen University, Sun Yat\u2010Sen University  Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lipeng","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine Shenzhen Campus of Sun Yat\u2010Sen University, Sun Yat\u2010Sen University  Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juntao","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine Shenzhen Campus of Sun Yat\u2010Sen University, Sun Yat\u2010Sen University  Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Duo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology The Seventh Affiliated Hospital, Sun Yat\u2010Sen University  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojiao","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine Shenzhen Campus of Sun Yat\u2010Sen University, Sun Yat\u2010Sen University  Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Tang","sequence":"additional","affiliation":[{"name":"Clinical Skills Training Center, School of Medicine Shenzhen Campus of Sun Yat\u2010Sen University, Sun Yat\u2010Sen University  Shenzhen Guangdong China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2545-4239","authenticated-orcid":false,"given":"Jiang\u2010Hong","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Pharmacology, Physiology &amp; Neuroscience, Rutgers The State University of New Jersey, New Jersey Medical School  Newark New Jersey USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao\u2010Yu","family":"Miao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Naval Medical University\/Second Military Medical University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7551-4618","authenticated-orcid":false,"given":"Rao","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, School of Medicine Shenzhen Campus of Sun Yat\u2010Sen University, Sun Yat\u2010Sen University  Shenzhen Guangdong China"},{"name":"Shenzhen Key Laboratory for Systems Medicine in Inflammatory Diseases, School of Medicine Shenzhen Campus of Sun Yat\u2010Sen University, Sun Yat\u2010Sen University  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2020.20091375"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pharmtox-031323-115847"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00043.2007"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4419-8056-4_10"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(00)00039-3"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-009-1710-5"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12888-025-07014-9"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/alcalc\/34.2.141"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.110.170928"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.90"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-3019-7"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-010-2092-4"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2015.07.012"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70225-4"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/jsr.14277"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.106.111039"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2013.03.018"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-025-03358-8"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2023.0162"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2022.112947"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2022_372"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1177\/0269881120961253"},{"issue":"9","key":"e_1_2_11_24_1","article-title":"Pitolisant and Other Histamine\u20103 Receptor Antagonists\u2010An Update on Therapeutic Potentials and Clinical Prospects","volume":"7","author":"Harwell V.","year":"2020","journal-title":"Medicines (Basel, Switzerland)"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/zsz252"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0306-4522(02)00135-5"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.03.011"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2019.107863"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01337-3"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-019-0378-8"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-023-01582-8"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2017.06.005"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12149"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/ALN.0b013e3181b061a0"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25052933"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2024.08.009"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41386-022-01482-3"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.279"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2018.01.033"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/adb.12528"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2023.01.018"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-820107-7.00023-9"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/7854_2023_424"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(16)00104-8"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/0741-8329(92)90004-T"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2284-07.2007"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2014.02.007"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14634"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2020.07.023"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2010.07.002"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/aps.2016.66"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2021.06.002"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1096\/fsb2fj000545fje"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-020-02111-0"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2023.114509"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1971"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/npp.2011.20"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dcn.2015.04.005"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.04.010"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0096232"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.70732","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cns.70732","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.70732","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T10:59:15Z","timestamp":1771153155000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns.70732"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/cns.70732"],"URL":"https:\/\/doi.org\/10.1002\/cns.70732","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-08-14","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-12-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70732"}}