{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T01:12:41Z","timestamp":1785028361464,"version":"3.55.0"},"reference-count":50,"publisher":"Elsevier BV","issue":"5","license":[{"start":{"date-parts":[[2013,5,1]],"date-time":"2013-05-01T00:00:00Z","timestamp":1367366400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Neuropsychopharmacology"],"published-print":{"date-parts":[[2013,5]]},"DOI":"10.1016\/j.euroneuro.2012.05.005","type":"journal-article","created":{"date-parts":[[2012,6,6]],"date-time":"2012-06-06T18:35:52Z","timestamp":1339007752000},"page":"400-412","source":"Crossref","is-referenced-by-count":80,"title":["Acute atorvastatin treatment exerts antidepressant-like effect in mice via the l-arginine\u2013nitric oxide\u2013cyclic guanosine monophosphate pathway and increases BDNF levels"],"prefix":"10.1016","volume":"23","author":[{"given":"Fabiana K.","family":"Ludka","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9a D.E.","family":"Zomkowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio P.","family":"Cunha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tharine","family":"Dal-Cim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana L\u00facia B.","family":"Zeni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana L\u00facia S.","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla I.","family":"Tasca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.euroneuro.2012.05.005_bib54","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/nature10130","article-title":"NMDA receptor blockade at rest triggers rapid bahavioural antidepressant responses","volume":"475","author":"Autry","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib1","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0091-3057(01)00599-8","article-title":"Intra- and interstrain differences in models of \u201cbehavioral despair\u201d","volume":"70","author":"Bai","year":"2001","journal-title":"Pharmacol. Biochem. Behav."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib2","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1111\/j.1471-4159.2004.02980.x","article-title":"Neuroprotective effects of atorvastatin against glutamate induced excitotoxicity in primary cortical neurons","volume":"92","author":"Bosel","year":"2005","journal-title":"J. Neurochem."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib3","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nrn1629","article-title":"Is mood chemistry?","volume":"6","author":"Castren","year":"2005","journal-title":"Nat. Rev. Neurosci."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib4","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.neuroscience.2006.06.002","article-title":"Examination of behavioral deficits triggered by targeting BDNF in fetal or postnatal brains of mice","volume":"142","author":"Chan","year":"2006","journal-title":"Neuroscience"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib5","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/sj.jcbfm.9600034","article-title":"Atorvastatin induction of VEGF and BDNF promotes brain plasticity after stroke in mice","volume":"25","author":"Chen","year":"2005","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib6","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1016\/j.pnpbp.2007.02.008","article-title":"Involvement of L-arginine\u2013nitric oxide\u2013cyclic guanosine monophosphate pathway in the antidepressant like effect of venlafaxine in mice","volume":"31","author":"Dhir","year":"2007","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib7","unstructured":"Drug Bank, \u3008http:\/\/www.drugbank.ca\/drugs\/DB00857\u3009. Update Date 2011-11-09."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib8","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1038\/sj.bjp.0704569","article-title":"NO as a signalling molecule in the nervous system","volume":"135","author":"Esplugues","year":"2002","journal-title":"Br. J. Pharmacol."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib9","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1021\/cn900006n","article-title":"Intercellular glutamate signaling in the nervous system and beyond","volume":"1","author":"Featherstone","year":"2010","journal-title":"ACS Chem. Neurosci."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib10","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.pnpbp.2007.07.027","article-title":"Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus","volume":"32","author":"Garcia","year":"2008","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib11","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/343425a0","article-title":"Regulation of the mevalonate pathway","volume":"343","author":"Goldstein","year":"1990","journal-title":"Nature"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib12","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1007\/s00406-005-0578-6","article-title":"Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients","volume":"255","author":"Gonul","year":"2005","journal-title":"Eur. Arch. Psychiatry Clin. Neurosci."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib13","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.brainresrev.2009.05.005","article-title":"Emerging role of glutamate in the pathophysiology of major depressive disorder","volume":"65","author":"Hashimoto","year":"2009","journal-title":"Brain Res. Rev."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib14","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1002\/j.2051-5545.2010.tb00298.x","article-title":"Pathophysiology of depression: do we have any solid evidence of interest to clinicians?","volume":"9","author":"Hasler","year":"2010","journal-title":"World Psychiatry"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib15","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/S0076-6879(94)33028-X","article-title":"Nitric-oxide synthase assays","volume":"233","author":"Hevel","year":"1994","journal-title":"Methods Enzymol."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib16","doi-asserted-by":"crossref","first-page":"903","DOI":"10.1089\/jpm.2010.9808","article-title":"Oral ketamine for the rapid treatment of depression and anxiety in patients receiving hospice care","volume":"17","author":"Irwin","year":"2010","journal-title":"J. Palliat. Med."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib17","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1006\/exnr.2002.7980","article-title":"Transplants of fibroblasts genetically modified to express BDNF promote axonal regeneration from supraspinal neurons following chronic spinal cord injury","volume":"1","author":"Jin","year":"2002","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib18","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1017\/S1461145705005316","article-title":"Involvement of nitric oxide\u2013cGMP pathway in the antidepressant like effects of adenosine in the forced swimming test","volume":"8","author":"Kaster","year":"2005","journal-title":"Int. J. Neuropsychopharmacol."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib19","doi-asserted-by":"crossref","first-page":"3719","DOI":"10.1002\/hbm.20801","article-title":"Brain volume abnormalities in major depressive disorder: a metaanalysis of magnetic resonance imaging studies","volume":"30","author":"Koolschijn","year":"2009","journal-title":"Hum. Brain Mapp."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib20","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.jad.2006.11.005","article-title":"Decreased plasma BDNF level in depressive patients","volume":"101","author":"Lee","year":"2007","journal-title":"J. Affect. Disord."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib22","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1126\/science.1190287","article-title":"mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists","volume":"329","author":"Li","year":"2010","journal-title":"Science"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib23","doi-asserted-by":"crossref","first-page":"822","DOI":"10.3171\/jns.2004.101.5.0822","article-title":"Atorvastatin reduction of intracranial hematoma volume in rats subjected to controlled cortical impact","volume":"101","author":"Lu","year":"2004","journal-title":"J. Neurosurg."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib24","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1038\/nn1971","article-title":"New insights into BDNF function in depression and anxiety","volume":"10","author":"Martinowich","year":"2007","journal-title":"Nat. Neurosci."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib25","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.pnpbp.2006.03.036","article-title":"Correlation between plasma levels of glutamate, alanine and serine with severity of depression","volume":"30","author":"Mitani","year":"2006","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib26","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.bbr.2011.07.024","article-title":"Involvement of nitric oxide\u2013cGMP pathway in the antidepressant-like effect of ascorbic acid in the tail suspension test","volume":"225","author":"Morreti","year":"2011","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib27","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s11064-007-9402-1","article-title":"Glutamate-induced toxicity in hippocampal slices involves apoptotic features and p38 MAPK signaling","volume":"33","author":"Molz","year":"2008","journal-title":"Neurochem. Res."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib28","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/0006-3223(87)90194-6","article-title":"A controlled trial of methylene blue in severe depressive illness","volume":"22","author":"Naylor","year":"1987","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib29","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1016\/S0002-9149(03)00820-8","article-title":"Safety of atorvastatin derived from analysis of 44 completed trials in 9,416 patients","volume":"15","author":"Newman","year":"2003","journal-title":"Am. J. Cardiol."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib30","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1196\/annals.1300.016","article-title":"Glutamate and depression: clinical and preclinical studies","volume":"1003","author":"Paul","year":"2003","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib31","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1016\/0003-2697(77)90043-4","article-title":"A simplification of the protein assay method of Lowry et al. which is more generally applicable","volume":"83","author":"Peterson","year":"1977","journal-title":"Anal. Biochem."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib32","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.expneurol.2010.08.030","article-title":"Atorvastatin prevents hippocampal cell death, neuroinflammation and oxidative stress following amyloid-\u03b21-40 administration in mice: evidence for dissociation between cognitive deficits and neuronal damage","volume":"226","author":"Piermartiri","year":"2010","journal-title":"Exp. Neurol."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib33","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1007\/s12640-009-9057-6","article-title":"Atorvastatin prevents hippocampal cell death due to quinolinic acid-induced seizures in mice by increasing Akt-phosphorylation and glutamate uptake","volume":"16","author":"Piermartiri","year":"2009","journal-title":"Neurotox. Res."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib34","doi-asserted-by":"crossref","unstructured":"Pittenger, C., Sanacora, G., Krystal, J.H. 2007. The NMDA receptor as a therapeutic target in major depressive disorder. CNS Neurol. Disord. Drug Targets. 6, 101\u2013115.","DOI":"10.2174\/187152707780363267"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib35","first-page":"327","article-title":"Behavioral despair in mice: a primary screening test for antidepressants","volume":"229","author":"Porsolt","year":"1977","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib37","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.pbb.2008.10.017","article-title":"Lovastatin potentiates the antidepressant efficacy of fluoxetine in rats","volume":"92","author":"Renshaw","year":"2009","journal-title":"Pharmacol. Biochem. Behav."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib38","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.bbr.2011.02.024","article-title":"Ketamine plus imipramine treatment induces antidepressant-like behavior and increases CREB and BDNF protein levels and PKA and PKC phosphorylation in rat brain","volume":"221","author":"R\u00e9us","year":"2011","journal-title":"Behav. Brain Res."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib40","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1038\/nrd2462","article-title":"Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders","volume":"7","author":"Sanacora","year":"2008","journal-title":"Nat. Rev. Drug Disc."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib41","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1034\/j.1399-5618.2003.00024.x","article-title":"Decreased hippocampal NMDA, but not kainate or AMPA receptors in bipolar disorder","volume":"5","author":"Scarr","year":"2003","journal-title":"Bipolar Disord."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib42","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1111\/j.1472-8206.2004.00299.x","article-title":"Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update","volume":"19","author":"Schachter","year":"2004","journal-title":"Fundam. Clin. Pharmacol."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib43","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1007\/BF00428203","article-title":"The tail suspension test: a new method for screening antidepressants in mice","volume":"85","author":"Steru","year":"1985","journal-title":"Psychopharmacology"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib45","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1016\/j.mehy.2006.09.043","article-title":"Statins may enhance the proteolytic cleavage of proBDNF: implications for the treatment of depression","volume":"68","author":"Tsai","year":"2007","journal-title":"Med. Hypotheses"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib46","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1101\/gad.11.18.2295","article-title":"Rho GTPases and signaling networks","volume":"11","author":"Van Aelst","year":"1997","journal-title":"Genes Dev."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib47","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1089\/neu.2007.0369","article-title":"Simvastatin-mediated upregulation of VEGF and BDNF, activation of the PI3K\/Akt pathway, and increase of neurogenesis are associated with therapeutic improvement after traumatic brain injury","volume":"25","author":"Wu","year":"2008","journal-title":"J. Neurotrauma"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib48","doi-asserted-by":"crossref","DOI":"10.1111\/j.1742-7843.2012.00877.x","article-title":"Inhibition of neuronal nitric oxide synthase and soluble guanylate cyclase prevents depression-like behaviour in rats exposed to chronic unpredictable mild stress","author":"Yazir","year":"2012","journal-title":"Basic Clin. Pharmacol. Toxicol"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib49","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/S0735-1097(03)00785-X","article-title":"Long-term statin use and psychological well-being","volume":"42","author":"Young-Xu","year":"2003","journal-title":"J. Am. Coll. Cardiol."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib50","doi-asserted-by":"crossref","first-page":"11104","DOI":"10.1523\/JNEUROSCI.23-35-11104.2003","article-title":"3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors protect cortical neurons from excitotoxicity","volume":"35","author":"Zacco","year":"2003","journal-title":"J. Neurosci."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib51","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1001\/archpsyc.63.8.856","article-title":"A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression","volume":"63","author":"Zarate","year":"2006","journal-title":"Arch. Gen. Psychiatry"},{"key":"10.1016\/j.euroneuro.2012.05.005_bib52","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1016\/j.jep.2011.07.009","article-title":"Antidepressant-like and neuroprotective effects of Aloysia gratissima: investigation of involvement of l-arginine\u2013nitric oxide\u2013cyclic guanosine monophosphate pathway","volume":"137","author":"Zeni","year":"2011","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.euroneuro.2012.05.005_bib53","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/j.euroneuro.2010.07.011","article-title":"Involvement of NMDA receptors and l-arginine\u2013nitric oxide\u2013cyclic guanosine monophosphate pathway in the antidepressant-like effects of escitalopram in the forced swimming test","volume":"20","author":"Zomkowski","year":"2010","journal-title":"Eur. Neurophychopharmacol."}],"container-title":["European Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0924977X1200140X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0924977X1200140X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2019,6,29]],"date-time":"2019-06-29T09:11:18Z","timestamp":1561799478000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0924977X1200140X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,5]]},"references-count":50,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2013,5]]}},"alternative-id":["S0924977X1200140X"],"URL":"https:\/\/doi.org\/10.1016\/j.euroneuro.2012.05.005","relation":{},"ISSN":["0924-977X"],"issn-type":[{"value":"0924-977X","type":"print"}],"subject":[],"published":{"date-parts":[[2013,5]]}}}