{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T01:27:54Z","timestamp":1777858074688,"version":"3.51.4"},"reference-count":68,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2011,10,30]],"date-time":"2011-10-30T00:00:00Z","timestamp":1319932800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Psychopharmacol"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:p>Preclinical and clinical studies indicate that deficiency in folic acid plays a role in the pathophysiology of depression. Considering that alterations in the signaling pathways that regulate neuroplasticity and cellular survival are implicated in depressive disorders, the present study investigated the involvement of the phosphoinositide 3-kinase (PI3K), glycogen synthase kinase-3 (GSK-3\u03b2), and peroxisome proliferator-activated receptor-\u03b3 (PPAR\u03b3) in the antidepressant-like effect of folic acid in the forced swimming test (FST). The intracerebroventricular (i.c.v.) pre-treatment of mice with LY294002 (10 nmol\/site, a PI3K inhibitor) or GW-9662 (1 \u00b5g\/site, a PPAR\u03b3 antagonist) prevented the antidepressant-like effect of folic acid (50 mg\/kg, p.o.) in the FST. In addition, the administration of subeffective doses of the selective GSK-3\u03b2 inhibitor, AR-A014418 (3 mg\/kg, i.p.), a non-selective GSK-3\u03b2 inhibitor, lithium chloride (10 mg\/kg, p.o) or a PPAR\u03b3 agonist, rosiglitazone (1 \u00b5g\/site, i.c.v.) in combination with a subeffective dose of folic acid (10 mg\/kg, p.o.) significantly reduced the immobility time in the FST as compared with either drug alone, without altering the locomotor activity. These results indicate that the antidepressant-like effect of folic acid in the FST might be dependent on inhibition of GSK-3\u03b2 and activation of PPAR\u03b3, reinforcing the notion that these are important targets for antidepressant activity.<\/jats:p>","DOI":"10.1177\/0269881111424456","type":"journal-article","created":{"date-parts":[[2011,10,30]],"date-time":"2011-10-30T20:33:12Z","timestamp":1320006792000},"page":"714-723","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":54,"title":["Involvement of PI3K, GSK-3\u03b2 and PPAR\u03b3 in the antidepressant-like effect of folic acid in the forced swimming test in mice"],"prefix":"10.1177","volume":"26","author":[{"given":"Josiane","family":"Budni","sequence":"first","affiliation":[{"name":"Universidade Federal de Santa Catarina, Departamento de Bioqu\u00edmica, Florian\u00f3polis, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly R","family":"Lobato","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Catarina, Departamento de Bioqu\u00edmica, Florian\u00f3polis, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ricardo W","family":"Binfar\u00e9","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Catarina, Departamento de Bioqu\u00edmica, Florian\u00f3polis, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andiara E","family":"Freitas","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Catarina, Departamento de Bioqu\u00edmica, Florian\u00f3polis, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Paula","family":"Costa","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Catarina, Departamento de Bioqu\u00edmica, Florian\u00f3polis, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Dolores","family":"Mart\u00edn-de-Saavedra","sequence":"additional","affiliation":[{"name":"Departamento de Farmacologia y Terap\u00eautica, Universidad Autonoma de Madrid, Madrid, Spain"},{"name":"Instituto Te\u00f3filo Hernando, Universidad Autonoma de Madrid, Madrid, Spain"},{"name":"HIV Unit, Hospital La Paz\/Aut\u00f3noma University School of Medicine, IdiPAZ, Universidad Autonoma de Madrid, Departamento de Farmacologia, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo B","family":"Leal","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Catarina, Departamento de Bioqu\u00edmica, Florian\u00f3polis, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela G","family":"Lopez","sequence":"additional","affiliation":[{"name":"Departamento de Farmacologia y Terap\u00eautica, Universidad Autonoma de Madrid, Madrid, Spain"},{"name":"Instituto Te\u00f3filo Hernando, Universidad Autonoma de Madrid, Madrid, Spain"},{"name":"HIV Unit, Hospital La Paz\/Aut\u00f3noma University School of Medicine, IdiPAZ, Universidad Autonoma de Madrid, Departamento de Farmacologia, Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana L\u00facia S","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Universidade Federal de Santa Catarina, Departamento de Bioqu\u00edmica, Florian\u00f3polis, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2011,10,30]]},"reference":[{"key":"bibr1-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpsychores.2006.07.007"},{"key":"bibr2-0269881111424456","doi-asserted-by":"publisher","DOI":"10.3109\/10401230209147396"},{"key":"bibr3-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.011008.145634"},{"key":"bibr4-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0711496105"},{"key":"bibr5-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1503\/jpn.110011"},{"key":"bibr6-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02422.x"},{"key":"bibr7-0269881111424456","first-page":"275","volume":"30","author":"Bourin M","year":"2005","journal-title":"J Psychiatry Neurosci"},{"key":"bibr8-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2004.03.006"},{"key":"bibr9-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2007.10.016"},{"key":"bibr10-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2008.08.033"},{"key":"bibr11-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2009.01.004"},{"key":"bibr12-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-5618.2010.00827.x"},{"key":"bibr13-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2007.08.010"},{"key":"bibr14-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2011.05.053"},{"key":"bibr15-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1126\/science.296.5573.1655"},{"key":"bibr16-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2000.0721327.x"},{"key":"bibr17-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-0327(00)00153-1"},{"key":"bibr18-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1177\/0269881105048899"},{"key":"bibr19-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1038\/378785a0"},{"key":"bibr20-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/S0165-6147(02)02017-5"},{"key":"bibr21-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2005.03.008"},{"key":"bibr22-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainres.2011.02.065"},{"key":"bibr23-0269881111424456","first-page":"649","volume":"20","author":"Desvergne B","year":"1999","journal-title":"Endocr Rev"},{"key":"bibr24-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1301641"},{"key":"bibr25-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1097\/FBP.0b013e328331b9bf"},{"key":"bibr26-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1177\/0269881109104845"},{"key":"bibr27-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)91942-4"},{"key":"bibr28-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1517\/14728222.10.3.377"},{"key":"bibr29-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300731"},{"key":"bibr30-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145704004535"},{"key":"bibr31-0269881111424456","doi-asserted-by":"publisher","DOI":"10.2174\/1389450110607011399"},{"key":"bibr32-0269881111424456","doi-asserted-by":"publisher","DOI":"10.4088\/JCP.v65n0103"},{"key":"bibr33-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/S0301-0082(01)00011-9"},{"key":"bibr34-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbapap.2003.11.009"},{"key":"bibr35-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2009.04.002"},{"key":"bibr36-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-07-02567.2000"},{"key":"bibr37-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2004.09.032"},{"key":"bibr38-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/0014-2999(89)90728-0"},{"key":"bibr39-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mp.4000494"},{"key":"bibr40-0269881111424456","doi-asserted-by":"publisher","DOI":"10.2174\/1389450110607011421"},{"key":"bibr41-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2004.01.008"},{"key":"bibr42-0269881111424456","first-page":"1","volume":"6","author":"Kalinichev M","year":"2011","journal-title":"Int J Neuropsychopharmacol"},{"key":"bibr43-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2006.12.018"},{"key":"bibr44-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.17.1.615"},{"key":"bibr45-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/S0028-3908(99)00169-0"},{"key":"bibr46-0269881111424456","doi-asserted-by":"publisher","DOI":"10.2174\/156652409787847146"},{"key":"bibr47-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1152\/jn.2002.87.5.2297"},{"key":"bibr48-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-5618.2002.40201.x"},{"key":"bibr49-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1038\/sj.npp.1300439"},{"key":"bibr50-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1017\/S1461145708009267"},{"key":"bibr51-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2004.08.030"},{"key":"bibr52-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2011.04.012"},{"key":"bibr53-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.ddmec.2004.11.020"},{"key":"bibr54-0269881111424456","first-page":"327","volume":"229","author":"Porsolt RD","year":"1977","journal-title":"Arch Int Pharmacodyn Ther"},{"key":"bibr55-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2010.32"},{"key":"bibr56-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1007\/s002130050846"},{"key":"bibr57-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbb.2005.08.003"},{"key":"bibr58-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/S0278-5846(02)00307-X"},{"key":"bibr59-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-4328(03)00069-X"},{"key":"bibr60-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.pnpbp.2008.05.020"},{"key":"bibr61-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2007.03.002"},{"key":"bibr62-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2009.00180.x"},{"key":"bibr63-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1007\/s002100000370"},{"key":"bibr64-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2009.06.015"},{"key":"bibr65-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1993.tb12879.x"},{"key":"bibr66-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1177\/0269881104042630"},{"key":"bibr67-0269881111424456","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M706954200"},{"key":"bibr68-0269881111424456","first-page":"w13071","volume":"140","author":"Yessoufou A","year":"2010","journal-title":"Swiss Med Wkly"}],"container-title":["Journal of Psychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0269881111424456","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0269881111424456","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0269881111424456","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:07:08Z","timestamp":1777507628000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0269881111424456"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,10,30]]},"references-count":68,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,5]]}},"alternative-id":["10.1177\/0269881111424456"],"URL":"https:\/\/doi.org\/10.1177\/0269881111424456","relation":{},"ISSN":["0269-8811","1461-7285"],"issn-type":[{"value":"0269-8811","type":"print"},{"value":"1461-7285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,10,30]]}}}