Sex and estrous cycle influence diazepam effects on anxiety and memory: Possible role of progesterone

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dc.citation.volume70
dc.contributor.authorSilva, Anatildes Feitosa
dc.contributor.authorSousa, Diego Silveira
dc.contributor.authorMedeiros, André de Macêdo [UNIFESP]
dc.contributor.authorMacedo, Priscila Tavares
dc.contributor.authorLeão, Anderson Henrique França Figueiredo
dc.contributor.authorRibeiro, Alessandra Mussi [UNIFESP]
dc.contributor.authorIzídio, Geison Souza
dc.contributor.authorSilva, Regina Helena [UNIFESP]
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.coverageOxford
dc.date.accessioned2020-07-31T12:47:35Z
dc.date.available2020-07-31T12:47:35Z
dc.date.issued2016
dc.description.abstractStudies with rodents and humans show the relationship between female sex hormones and cognitive/emotional tasks. However, despite the greater incidence of anxiety disorders in women, the data are still inconclusive regarding the mechanisms related to this phenomenon. We evaluated the effects of a classical anxiolytic/amnestic drug (diazepam; DZP) on female (at different estrous cycle phases) and male rats tested in the plus-maze discriminative avoidance task (PMDAT), that allows the concomitant evaluation of memory and anxiety-like behavior. Further, in order to investigate the role of progesterone and its metabolites in the effects of DZP in the PMDAT, female rats were pre-treated with the progesterone receptor antagonist mifepristone or the 5-alpha-reductase inhibitor finasteride. The main findings were: (1) DZP caused memory impairment and anxiolysis in both sexes, but only the highest dose induced the anxiolytic effect in females; (2) females in proestrus did not present the amnestic and anxiolytic effects of DZP (at 2.0 and 4.0 mg/kg, respectively) and (3) the co-administration of mifepristone reestablished both amnestic and anxiolytic effects of DZP, while finasteride reinstated the amnestic effect in proestrus female rats. These results suggest that changes in the endogenous levels of progesterone and its metabolites are important in the modulation of emotional/cognitive behavior in female rats. Based on the influence on different aspects of DZP action, the mechanisms related to this modulation are probably linked to GABAergic transmission, but this point remains to be investigated. Further, the variation in therapeutic and adverse effects of DZP depending on sex and hormonal state is of great relevance considering the higher prevalence of anxiety disorders in women.en
dc.description.affiliationUniv Fed Rio Grande do Norte, Dept Physiol, Memory Studies Lab, Natal, RN, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Pharmacol, Lab Behav Neurosci, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Biosci, Lab Neurosci & Bioprospecting Nat Prod, Santos, Brazil
dc.description.affiliationUniv Fed Santa Catarina, Cell Biol Embryol & Genet Dept, Lab Behav Genet, Florianopolis, SC, Brazil
dc.description.affiliationUnifespLaboratory of Behavioral Neuroscience, Pharmacology Department, Universidade Federal de São Paulo, São Paulo, Brazil
dc.description.affiliationUnifespLaboratory of Neuroscience and Bioprospecting of Natural Products, Biosciences Department, Universidade Federal de São Paulo, Santos, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)pt
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)pt
dc.description.sponsorshipIDCNPq: 310513/2014-6pt
dc.format.extent68-76
dc.identifierhttps://dx.doi.org/10.1016/j.pnpbp.2016.05.003
dc.identifier.citationProgress In Neuro-Psychopharmacology & Biological Psychiatry. Oxford, v. 70, p. 68-76, 2016.
dc.identifier.doi10.1016/j.pnpbp.2016.05.003
dc.identifier.issn0278-5846
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/56916
dc.identifier.wosWOS:000378854200008
dc.language.isoeng
dc.publisherPergamon-Elsevier Science Ltd
dc.relation.ispartofProgress In Neuro-Psychopharmacology & Biological Psychiatry
dc.rightsinfo:eu-repo/semantics/restrictedAccess
dc.subjectLearning/memoryen
dc.subjectAnxiety-like behavioren
dc.subjectMifepristoneen
dc.subjectFinasterideen
dc.subjectSex differences, progesteroneen
dc.titleSex and estrous cycle influence diazepam effects on anxiety and memory: Possible role of progesteroneen
dc.typeinfo:eu-repo/semantics/article
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