{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:28:34Z","timestamp":1792024114817,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2024,9,5]],"date-time":"2024-09-05T00:00:00Z","timestamp":1725494400000},"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":["82304462"],"award-info":[{"award-number":["82304462"]}],"id":[{"id":"10.13039\/501100001809","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":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The emerging antidepressant effects of ketamine have inspired tremendous interest in its underlying neurobiological mechanisms, although the involvement of 5\u2010HT in the antidepressant effects of ketamine remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach<\/jats:title><jats:p>The chronic restraint stress procedure was performed to induce depression\u2010like behaviours in mice. OFT, FST, TST, and NSFT tests were used to evaluate the antidepressant\u2010like effects of ketamine. <jats:italic>Tph2<\/jats:italic> knockout or depletion of 5\u2010HT by PCPA and 5,7\u2010DHT were used to manipulate the brain 5\u2010HT system. ELISA and fibre photometry recordings were used to measure extracellular 5\u2010HT levels in the brain.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>60\u2009min after injection, ketamine (10\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>, i.p.) produced rapid antidepressant\u2010like effects and increased brain 5\u2010HT levels. After 24\u2009h, ketamine significantly reduced immobility time in TST and FST tests and increased brain 5\u2010HT levels, as measured by ELISA and fibre photometry recordings. The sustained (24\u2009h) but not rapid (60\u2009min) antidepressant\u2010like effects of ketamine were abrogated by PCPA and 5,7\u2010DHT, or by <jats:italic>Tph2<\/jats:italic> knockout. Importantly, NBQX (10\u00a0mg\u00b7kg<jats:sup>\u22121<\/jats:sup>, i.p.), an AMPA receptor antagonist, significantly inhibited the effect of ketamine on brain 5\u2010HT levels and abolished the sustained antidepressant\u2010like effects of ketamine in na\u00efve or CRS\u2010treated mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion and Implications<\/jats:title><jats:p>This study confirms the requirement of serotonergic neurotransmission for the sustained antidepressant\u2010like effects of ketamine, which appears to involve AMPA receptors, and provides avenues to search for antidepressant pharmacological targets.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.17324","type":"journal-article","created":{"date-parts":[[2024,9,6]],"date-time":"2024-09-06T06:09:51Z","timestamp":1725602991000},"page":"4874-4889","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Serotonergic transmission plays differentiated roles in the rapid and sustained antidepressant\u2010like effects of ketamine"],"prefix":"10.1111","volume":"181","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3045-5543","authenticated-orcid":false,"given":"Yong\u2010Yu","family":"Yin","sequence":"first","affiliation":[{"name":"Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures Beijing Key Laboratory of Neuropsychopharmacology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7078-7871","authenticated-orcid":false,"given":"Jiao\u2010Zhao","family":"Yan","sequence":"additional","affiliation":[{"name":"Beijing Institute of Basic Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian\u2010Qian","family":"Wei","sequence":"additional","affiliation":[{"name":"School of Medicine Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si\u2010Rui","family":"Sun","sequence":"additional","affiliation":[{"name":"Beijing Ditan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Qiang","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Laboratory Animal Science Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9071-8985","authenticated-orcid":false,"given":"Li\u2010Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures Beijing Key Laboratory of Neuropsychopharmacology  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun\u2010Feng","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Institute of Pharmacology and Toxicology, State Key Laboratory of Toxicology and Medical Countermeasures Beijing Key Laboratory of Neuropsychopharmacology  Beijing China"},{"name":"Beijing Institute of Basic Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15537"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyz041"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2021.08.003"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14112"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0006-3223(99)00230-9"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/bf00181937"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22041927"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2012.05.018"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2005.03.009"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15868"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.09m05327blu"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-020-00916-y"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jphs.2014.09.003"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rpsmen.2022.06.008"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2007.05577.x"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2009.11.007"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-3024-x"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(85)90153-4"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1385\/nmm:5:1:027"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043157"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euroneuro.2008.12.005"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12283"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00868-8"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2017.03.007"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2010.06.015"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2002.02037.x"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2010.12.015"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15178"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph3010019"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.091199"},{"key":"e_1_2_12_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD011611.pub2"},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.2011.244"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2015.09.010"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1176\/appi.ajp.2015.15040465"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.1017\/s1461145714000649"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-022-02543-6"},{"key":"e_1_2_12_38_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000410"},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2019.02.017"},{"key":"e_1_2_12_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2016.05.010"},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-30386-5"},{"key":"e_1_2_12_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0197-0186(03)00104-9"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2008.04.016"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ibror.2017.11.001"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1177\/23982128221081645"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-021-00823-7"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11617"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2016.12.045"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.3791\/52587"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108573"},{"key":"e_1_2_12_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2019.02.048"},{"key":"e_1_2_12_52_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpsyc.63.8.856"},{"key":"e_1_2_12_53_1","doi-asserted-by":"publisher","DOI":"10.1093\/ijnp\/pyx100"},{"key":"e_1_2_12_54_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2012.04198.x"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.17324","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,4]],"date-time":"2024-11-04T06:25:33Z","timestamp":1730701533000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.17324"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,9,5]]},"references-count":53,"journal-issue":{"issue":"23","published-print":{"date-parts":[[2024,12]]}},"alternative-id":["10.1111\/bph.17324"],"URL":"https:\/\/doi.org\/10.1111\/bph.17324","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,9,5]]},"assertion":[{"value":"2023-09-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-06-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-09-05","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}