Successful Combined Therapy with Tamoxifen and Lithium in a Paradoxical Sleep Deprivation-Induced Mania Model

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dc.contributor.authorArmani, Fernanda [UNIFESP]
dc.contributor.authorAndersen, Monica L. [UNIFESP]
dc.contributor.authorAndreatini, Roberto
dc.contributor.authorFrussa-Filho, Roberto [UNIFESP]
dc.contributor.authorTufik, Sergio [UNIFESP]
dc.contributor.authorFernandes Galduroz, Jose Carlos [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniv Fed Parana
dc.date.accessioned2016-01-24T14:17:36Z
dc.date.available2016-01-24T14:17:36Z
dc.date.issued2012-01-01
dc.description.abstractBackground: Previous studies have suggested that manic states and sleep deprivation could contribute to the pathophysiology of bipolar disorder (BD) through protein kinase C (PKC) signaling abnormalities. Moreover, adjunctive therapy has become a standard strategy in the management of BD patients who respond poorly to current pharmacological treatments. Aim: Thus, the aim of this study was to investigate the possible involvement of PKC inhibition by tamoxifen both separately or in combination with lithium, in paradoxical sleep deprivation (PSD)-induced hyperactivity, one facet of mania-like behavior. Materials & Methods: Adult male C57BL/6J mice were randomly distributed (n = 7/group) in 24-h PSD or control groups and injected intraperitoneally (i.p.) with vehicle, lithium (50, 100, or 150 mg/kg) or tamoxifen (0.5, 1.0, or 2.0 mg/kg experiment 1). in a second experiment, mice were injected i.p. with vehicle or a combination of subeffective doses of lithium and tamoxifen. Animals were subjected to a protocol based on repetitive PSD conditions, followed by assessment of locomotion activity in the open-field task. Results: PSD significantly increased locomotor activity in both experiments. These behavioral changes were prevented by a treatment with lithium or tamoxifen, or a combined treatment with both lithium and tamoxifen. Discussion: Therefore, our findings suggest that lithium and tamoxifen exert reversal effects against PSD-induced hyperactivity in mice. Conclusion: Furthermore, tamoxifen as an adjunct to lithium therapy provides support for an alternative treatment of individuals who either do not respond adequately or cannot tolerate the adverse effects associated with therapeutic doses of lithium.en
dc.description.affiliationUniversidade Federal de São Paulo UNIFESP, Dept Psicobiol, São Paulo, Brazil
dc.description.affiliationUniv Fed Parana, Setor Ciencias Biol, Dept Farmacol, BR-80060000 Curitiba, Parana, Brazil
dc.description.affiliationUniversidade Federal de São Paulo UNIFESP, Dept Farmacol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo UNIFESP, Dept Psicobiol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo UNIFESP, Dept Farmacol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipAssociacao Fundo de Incentivo a Psicofarmacologia (AFIP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIDFAPESP: 98/14303-3
dc.format.extent119-125
dc.identifierhttp://dx.doi.org/10.1111/j.1755-5949.2010.00224.x
dc.identifier.citationCns Neuroscience & Therapeutics. Hoboken: Wiley-Blackwell, v. 18, n. 2, p. 119-125, 2012.
dc.identifier.doi10.1111/j.1755-5949.2010.00224.x
dc.identifier.issn1755-5930
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/34356
dc.identifier.wosWOS:000300001700004
dc.language.isoeng
dc.publisherWiley-Blackwell
dc.relation.ispartofCns Neuroscience & Therapeutics
dc.rightsinfo:eu-repo/semantics/openAccess
dc.rights.licensehttp://olabout.wiley.com/WileyCDA/Section/id-406071.html
dc.subjectAdjunctive therapyen
dc.subjectLithiumen
dc.subjectManiaen
dc.subjectMiceen
dc.subjectParadoxical sleep deprivationen
dc.subjectProtein kinase Cen
dc.subjectTamoxifenen
dc.titleSuccessful Combined Therapy with Tamoxifen and Lithium in a Paradoxical Sleep Deprivation-Induced Mania Modelen
dc.typeinfo:eu-repo/semantics/article
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