{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T18:51:54Z","timestamp":1790189514745,"version":"4.1.0"},"reference-count":42,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T00:00:00Z","timestamp":1622764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["19K10680"],"award-info":[{"award-number":["19K10680"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology","doi-asserted-by":"publisher","award":["20H03955"],"award-info":[{"award-number":["20H03955"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>The purpose of this study is to examine the effect of repeated cocaine administration on the whole body of rats. Rats (male, 6 weeks old, Sprague Dawley) were injected intraperitoneally with cocaine (50 mg\/kg) once a day for 1, 3 or 7 days, and major organs (heart, liver, lung, brain, kidney, spleen) were excised from the sacrificed animals. During autopsy, we found a reduction in spleen size, but not other organs, in cocaine-administered rats as compared to control rats. This reduction became to be noticed at 3 day and easily perceived at 7 day. No marked changes were observed in other organs examined. H&amp;E and EMG staining showed a tendency for a decrease in the number of red blood cells (RBCs) as well as an increase in collagen fibers in the spleens of rats treated repeatedly with cocaine. Transcriptome analysis indicated that repeated cocaine administration depletes RBCs from the spleen. Immunoblot analysis showed that cocaine increases the phosphorylation of myosin light chain (MYL) as well as the levels of transgelin, both of which are involved in the contraction of myofibrils. Collectively, these results show that repeated cocaine administration results in sustained contraction of the spleen, which leads to the release of RBCs from the spleen into circulation.<\/jats:p>","DOI":"10.1371\/journal.pone.0252853","type":"journal-article","created":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T18:56:30Z","timestamp":1622832990000},"page":"e0252853","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Sustained splenic contraction after daily cocaine administration in rats"],"prefix":"10.1371","volume":"16","author":[{"given":"Moeka","family":"Nomura","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Unuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4410-6432","authenticated-orcid":true,"given":"Toshihiko","family":"Aki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Uemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,6,4]]},"reference":[{"issue":"10","key":"pone.0252853.ref001","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1111\/add.14234","article-title":"Global statistics on alcohol, tobacco and illicit drug use: 2017 status report","volume":"113","author":"A Peacock","year":"2018","journal-title":"Addiction"},{"issue":"3","key":"pone.0252853.ref002","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/S0740-5472(01)00192-1","article-title":"Cocaine dependence: a disease of the brain\u2019s reward centers","volume":"21","author":"CA Dackis","year":"2001","journal-title":"J Subst Abuse Treat"},{"key":"pone.0252853.ref003","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/978-1-4899-1648-8_17","article-title":"Cardiovascular complications of cocaine abuse","volume":"10","author":"JA Perper","year":"1992","journal-title":"Recent Dev Alcohol"},{"issue":"1","key":"pone.0252853.ref004","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/0014-2999(76)90111-4","article-title":"Uptake and release of catecholamines in sympathetic nerve fibres in the spleen of the cod, Gadus morhua","volume":"39","author":"S Nilsson","year":"1976","journal-title":"Eur J Pharmacol"},{"issue":"1","key":"pone.0252853.ref005","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.jacc.2017.05.014","article-title":"The Cardiovascular Effects of Cocaine","volume":"70","author":"O Havakuk","year":"2017","journal-title":"Journal of the American College of Cardiology"},{"issue":"24","key":"pone.0252853.ref006","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1161\/CIRCULATIONAHA.110.940569","article-title":"Cardiovascular effects of cocaine","volume":"122","author":"BG Schwartz","year":"2010","journal-title":"Circulation"},{"issue":"6","key":"pone.0252853.ref007","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/S0147-9563(97)90040-6","article-title":"Cocaine: pathophysiology and clinical toxicology","volume":"26","author":"MS Boghdadi","year":"1997","journal-title":"Heart Lung"},{"issue":"2","key":"pone.0252853.ref008","first-page":"463","article-title":"Pulmonary edema in cocaine smokers","volume":"172","author":"CK Hoffman","year":"1989","journal-title":"RadiologyEpub 1989"},{"issue":"2","key":"pone.0252853.ref009","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1177\/014107680609900203","article-title":"Life threatening abdominal complications following cocaine abuse","volume":"99","author":"A Tiwari","year":"2006","journal-title":"J R Soc Med"},{"issue":"3","key":"pone.0252853.ref010","doi-asserted-by":"crossref","first-page":"868","DOI":"10.4081\/cp.2016.868","article-title":"Cocaine Use and Splenic Rupture: A Rare Yet Serious Association","volume":"6","author":"N Karthik","year":"2016","journal-title":"Clin Pract"},{"issue":"6","key":"pone.0252853.ref011","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/j.clinimag.2015.06.012","article-title":"Atraumatic splenic rupture and ileal volvulus following cocaine abuse","volume":"39","author":"DH Ballard","year":"2015","journal-title":"Clin Imaging"},{"issue":"3","key":"pone.0252853.ref012","first-page":"rjx054","article-title":"Cocaine-induced splenic rupture","volume":"2017","author":"AN Khan","year":"2017","journal-title":"J Surg Case Rep"},{"issue":"1","key":"pone.0252853.ref013","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1097\/00000658-199001000-00003","article-title":"Acute gastroduodenal perforations associated with use of crack","volume":"211","author":"HS Lee","year":"1990","journal-title":"Ann Surg"},{"issue":"9","key":"pone.0252853.ref014","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1097\/00007611-200009000-00015","article-title":"Cocaine-associated ischemic colitis","volume":"93","author":"JD Linder","year":"2000","journal-title":"South Med J"},{"issue":"9","key":"pone.0252853.ref015","first-page":"1558","article-title":"Ischemic colitis related to cocaine abuse","volume":"89","author":"DN Brown","year":"1994","journal-title":"Am J Gastroenterol"},{"issue":"1","key":"pone.0252853.ref016","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1159\/000185585","article-title":"Acute renal failure following cocaine abuse","volume":"52","author":"P Singhal","year":"1989","journal-title":"Nephron"},{"issue":"3","key":"pone.0252853.ref017","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1159\/000185869","article-title":"Acute renal failure and rhabdomyolysis following cocaine abuse","volume":"54","author":"F Ahijado","year":"1990","journal-title":"Nephron"},{"issue":"5","key":"pone.0252853.ref018","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1007\/BF02284256","article-title":"Biomechanisms of cocaine-induced hepatocyte injury mediated by the formation of reactive metabolites","volume":"65","author":"UA Boelsterli","year":"1991","journal-title":"Arch Toxicol"},{"issue":"5","key":"pone.0252853.ref019","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1016\/j.immuni.2013.10.010","article-title":"The spleen in local and systemic regulation of immunity","volume":"39","author":"V Bronte","year":"2013","journal-title":"Immunity"},{"issue":"5","key":"pone.0252853.ref020","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1080\/01926230600867743","article-title":"Normal structure, function, and histology of the spleen","volume":"34","author":"MF Cesta","year":"2006","journal-title":"Toxicol Pathol"},{"issue":"4","key":"pone.0252853.ref021","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1055\/s-0030-1255063","article-title":"The hematocrit paradox\u2014how does blood doping really work?","volume":"32","author":"D Boning","year":"2011","journal-title":"Int J Sports Med"},{"issue":"6","key":"pone.0252853.ref022","doi-asserted-by":"crossref","first-page":"361","DOI":"10.2165\/00007256-200232060-00002","article-title":"The human spleen during physiological stress","volume":"32","author":"IB Stewart","year":"2002","journal-title":"Sports Med"},{"issue":"5","key":"pone.0252853.ref023","doi-asserted-by":"crossref","first-page":"2071","DOI":"10.1152\/japplphysiol.00055.2001","article-title":"The human spleen as an erythrocyte reservoir in diving-related interventions","volume":"92","author":"K Espersen","year":"2002","journal-title":"J Appl Physiol (1985)"},{"issue":"3","key":"pone.0252853.ref024","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1152\/jappl.1993.74.3.1024","article-title":"Spleen emptying and venous hematocrit in humans during exercise","volume":"74","author":"M Laub","year":"1993","journal-title":"J Appl Physiol (1985)"},{"key":"pone.0252853.ref025","article-title":"Spleen contraction elevates hemoglobin concentration at high altitude during rest and exercise","author":"E Schagatay","year":"2020","journal-title":"European Journal of Applied Physiology"},{"key":"pone.0252853.ref026","doi-asserted-by":"crossref","first-page":"647","DOI":"10.3389\/fphys.2020.00647","article-title":"Spleen Size and Function in Sherpa Living High, Sherpa Living Low and Nepalese Lowlanders","volume":"11","author":"P Holmstrom","year":"2020","journal-title":"Front Physiol"},{"issue":"4","key":"pone.0252853.ref027","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1152\/jappl.2001.90.4.1623","article-title":"Selected contribution: role of spleen emptying in prolonging apneas in humans","volume":"90","author":"E Schagatay","year":"2001","journal-title":"J Appl Physiol (1985)"},{"issue":"4","key":"pone.0252853.ref028","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1007\/s002130050358","article-title":"Binge cocaine self-administration in humans: intravenous cocaine","volume":"132","author":"AS Ward","year":"1997","journal-title":"Psychopharmacology (Berl)"},{"issue":"1","key":"pone.0252853.ref029","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.pbb.2008.11.002","article-title":"Sensitivity to cocaine conditioned reward depends on sex and age","volume":"92","author":"E Zakharova","year":"2009","journal-title":"Pharmacol Biochem Behav"},{"issue":"Suppl","key":"pone.0252853.ref030","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0922-3371(88)90104-9","article-title":"Identification of a gene family of cadherin cell adhesion molecules","volume":"25","author":"M Takeichi","year":"1988","journal-title":"Cell Differ Dev"},{"issue":"Pt 1","key":"pone.0252853.ref031","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/bj3260001","article-title":"Caspases: the executioners of apoptosis","volume":"326","author":"GM Cohen","year":"1997","journal-title":"Biochem J"},{"issue":"2","key":"pone.0252853.ref032","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.cell.2009.07.006","article-title":"RIP kinases at the crossroads of cell death and survival","volume":"138","author":"W Declercq","year":"2009","journal-title":"Cell"},{"issue":"7575","key":"pone.0252853.ref033","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1038\/nature15541","article-title":"Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling","volume":"526","author":"N Kayagaki","year":"2015","journal-title":"Nature"},{"issue":"12","key":"pone.0252853.ref034","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1038\/ncb3064","article-title":"Inactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice","volume":"16","author":"JP Friedmann Angeli","year":"2014","journal-title":"Nat Cell Biol"},{"issue":"1\u20134","key":"pone.0252853.ref035","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1152\/advances.2003.27.4.201","article-title":"Smooth muscle contraction and relaxation","volume":"27","author":"RC Webb","year":"2003","journal-title":"Adv Physiol Educ"},{"issue":"3","key":"pone.0252853.ref036","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.biocel.2008.02.011","article-title":"Transgelin: an actin-binding protein and tumour suppressor","volume":"41","author":"SJ Assinder","year":"2009","journal-title":"Int J Biochem Cell Biol"},{"issue":"2","key":"pone.0252853.ref037","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1111\/bjh.12950","article-title":"The spleen and sickle cell disease: the sick(led) spleen","volume":"166","author":"V Brousse","year":"2014","journal-title":"Br J Haematol"},{"issue":"5","key":"pone.0252853.ref038","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1152\/jappl.1998.85.5.1877","article-title":"Cocaine administration induces human splenic constriction and altered hematologic parameters","volume":"85","author":"MJ Kaufman","year":"1998","journal-title":"J Appl Physiol (1985)"},{"issue":"6","key":"pone.0252853.ref039","first-page":"624","article-title":"The Laboratory Rat: Relating Its Age With Human\u2019s","volume":"4","author":"P Sengupta","year":"2013","journal-title":"Int J Prev Med"},{"key":"pone.0252853.ref040","first-page":"196","article-title":"Adolescent-onset vs. adult-onset cocaine use: Impact on cognitive functioning in animal models and opportunities for translation","author":"KM Kantak","year":"2020","journal-title":"Pharmacology Biochemistry and Behavior"},{"issue":"1","key":"pone.0252853.ref041","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.yhbeh.2009.12.003","article-title":"Estradiol: a key biological substrate mediating the response to cocaine in female rats","volume":"58","author":"AC Segarra","year":"2010","journal-title":"Horm Behav"},{"issue":"2","key":"pone.0252853.ref042","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0306-3623(02)00129-5","article-title":"Estrogen and vascular function","volume":"38","author":"RE White","year":"2002","journal-title":"Vascul Pharmacol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0252853","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,4]],"date-time":"2021-06-04T18:57:13Z","timestamp":1622833033000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0252853"}},"subtitle":[],"editor":[{"given":"Kanhaiya","family":"Singh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,6,4]]},"references-count":42,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,6,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0252853","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,4]]}}}