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

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

Author Silva, Anatildes Feitosa Google Scholar
Sousa, Diego Silveira Google Scholar
Medeiros, Andre Macedo Autor UNIFESP Google Scholar
Macedo, Priscila Tavares Google Scholar
Leao, Anderson Henrique Google Scholar
Ribeiro, Alessandra Mussi Autor UNIFESP Google Scholar
Izidio, Geison Souza Google Scholar
Silva, Regina Helena Autor UNIFESP Google Scholar
Abstract Studies 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 itsmetabolites 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. (C) 2016 Elsevier Inc. All rights reserved.
Keywords Learning/memory
Anxiety-like behavior
Mifepristone
Finasteride
Sex differences, progesterone
xmlui.dri2xhtml.METS-1.0.item-coverage Oxford
Language English
Sponsor Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Grant number CNPq: 310513/2014-6
Date 2016
Published in Progress In Neuro-Psychopharmacology & Biological Psychiatry. Oxford, v. 70, p. 68-76, 2016.
ISSN 0278-5846 (Sherpa/Romeo, impact factor)
Publisher Pergamon-Elsevier Science Ltd
Extent 68-76
Origin http://dx.doi.org/10.1016/j.pnpbp.2016.05.003
Access rights Closed access
Type Article
Web of Science ID WOS:000378854200008
URI https://repositorio.unifesp.br/handle/11600/56916

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