Effect of lithium on behavioral disinhibition induced by electrolytic lesion of the median raphe nucleus

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dc.contributor.authorPezzato, Fernanda A.
dc.contributor.authorCan, Adem
dc.contributor.authorHoshino, Katsumasa [UNESP]
dc.contributor.authorHorta, Jose de Anchieta C. [UNESP]
dc.contributor.authorMijares, Miriam G.
dc.contributor.authorGould, Todd D.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniv Maryland
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2015-10-21T13:11:14Z
dc.date.available2015-10-21T13:11:14Z
dc.date.issued2015-04-01
dc.description.abstractAlterations in brainstem circuits have been proposed as a possible mechanism underlying the etiology of mood disorders. Projections from the median raphe nucleus (MnR) modulate dopaminergic activity in the forebrain and are also part of a behavioral disinhibition/inhibition system that produces phenotypes resembling behavioral variations manifested during manic and depressive phases of bipolar disorder.The aim of this study is to assess the effect of chronic lithium treatment on behavioral disinhibition induced by MnR lesions.MnR electrolytic lesions were performed in C57BL/6J mice, with sham-operated and intact animals as control groups. Following recovery, mice were chronically treated with lithium (LiCl, added in chow) followed by behavioral testing.MnR lesion induced manic-like behavioral alterations including hyperactivity in the open field (OF), stereotyped circling, anxiolytic/risk taking in the elevated plus maze (EPM) and light/dark box (LDB) tests, and increased basal body temperature. Lithium was specifically effective in reducing OF hyperactivity and stereotypy but did not reverse (EPM) or had a nonspecific effect (LDB) on anxiety/risk-taking measures. Additionally, lithium decreased saccharin preference and prevented weight loss during single housing.Our data support electrolytic lesions of the MnR as an experimental model of a hyper-excitable/disinhibited phenotype consistent with some aspects of mania that are attenuated by the mood stabilizer lithium. Given lithium's relatively specific efficacy in treating mania, these data support the hypothesis that manic symptoms derive not only from the stimulation of excitatory systems but also from inactivation or decreased activity of inhibitory mechanisms.en
dc.description.affiliationUniv Sao Paulo, Inst Psicol, BR-05508900 Sao Paulo, Brazil
dc.description.affiliationUniv Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA
dc.description.affiliationUniv Estadual Paulista, Dept Fisiol, Inst Biociencias, BR-18618000 Botucatu, SP, Brazil
dc.description.affiliationUniv Estadual Paulista, Dept Anat, Inst Biociencias, BR-18618970 Botucatu, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Dept Expt Psychol, Sao Paulo, SP, Brazil
dc.description.affiliationSao Paulo State Univ, Dept Physiol, Botucatu, SP, Brazil
dc.description.affiliationSao Paulo State Univ, Dept Anat, Botucatu, SP, Brazil
dc.description.affiliationUniv Maryland, Sch Med, Dept Anat &Neurobiol, Baltimore, MD 21201 USA
dc.description.affiliationUniv Maryland, Sch Med, Dept Pharmacol, Baltimore, MD 21201 USA
dc.description.affiliationUnespUniv Estadual Paulista, Departamento de Fisiologia, Inst Biociencias, BR-18618000 Botucatu, SP, Brazil
dc.description.affiliationUnespUniv Estadual Paulista, Departametno de Anatomia, Inst Biociencias, BR-18618970 Botucatu, SP, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Departamento de Fisiologia, Botucatu, SP, Brazil
dc.description.affiliationUnespSao Paulo State Univ, Dept Anat, Botucatu, SP, Brazil
dc.description.sponsorshipMH091816
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorshipIdCNPq: 140649/2010-7
dc.description.sponsorshipIdCAPES: 13751/12-3
dc.format.extent1441-1450
dc.identifierhttp://link.springer.com/article/10.1007%2Fs00213-014-3775-z
dc.identifier.citationPsychopharmacology. New York: Springer, v. 232, n. 8, p. 1441-1450, 2015.
dc.identifier.doi10.1007/s00213-014-3775-z
dc.identifier.issn0033-3158
dc.identifier.urihttp://hdl.handle.net/11449/128586
dc.identifier.wosWOS:000352294200009
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofPsychopharmacology
dc.relation.ispartofjcr3.222
dc.relation.ispartofsjr1,494
dc.rights.accessRightsAcesso restrito
dc.sourceWeb of Science
dc.subjectBipolar disorderen
dc.subjectManiaen
dc.subjectAnimal modelen
dc.subjectLithiumen
dc.subjectMedian raphe nucleusen
dc.titleEffect of lithium on behavioral disinhibition induced by electrolytic lesion of the median raphe nucleusen
dc.typeArtigo
dcterms.licensehttp://www.springer.com/open+access/authors+rights?SGWID=0-176704-12-683201-0
dcterms.rightsHolderSpringer
unesp.author.orcid0000-0003-3639-9861[4]
unesp.author.orcid0000-0002-8023-5445[5]
unesp.campusUniversidade Estadual Paulista (Unesp), Instituto de Biociências, Botucatupt

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