title: Hormonal changes and increased anxiety-like behavior in a perimenopause-animal model induced by 4-vinylcyclohexene diepoxide (VCD) in female rats.
abstract: Perimenopause, a transition period that precedes menopause, is characterized by neuroendocrine, metabolic and behavioral changes, and is associated with increased vulnerability to affective disorders. The decrease in ovarian follicles during perimenopause contributes to a dynamic and complex hormonal milieu that is not yet well characterized. In rodents, 4-vinylcyclohexene diepoxide (VCD) induces a gradual depletion of ovarian follicles, modeling the transition to menopause in women. This study was aimed to investigate, in VCD-treated rats, the hormonal status and the behavior in the elevated plus-maze (EPM), a widely used test to assess anxiety-like behavior. From the postnatal day 28, rats were treated with VCD or vehicle for 15 days. At 80±5 days after the beginning of treatment the experiments were performed at proestrus and diestrus. In the first experiment rats were decapitated, ovary was collected and blood samples were taken for estradiol, progesterone, follicle stimulant hormone (FSH), testosterone, dihydrotestosterone (DHT) and corticosterone measurements. In the second experiment, rats were subjected to the EPM for 5 min, and behavioral categories recorded. Administration of VCD induced follicular depletion as well as an increase of the number of atretic follicles demonstrating the treatment efficacy. The transitional follicular depletion was accompanied by lower progesterone, testosterone and DHT with no changes in the FSH, estradiol and corticosterone plasma levels. On the EPM, rats showed decreased open arm exploration and increased risk assessment behavior, indicating increased anxiety. These findings show that administration of VCD to induce ovarian failure results in endocrine and anxiety-related changes that are similar to the symptoms exhibited by women during menopause transition. Thus, this model seems to be promising in the study of perimenopause-related changes.
authors: Laboratório de Neuropsicofarmacologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, 14049-901 Ribeirão Preto, SP, Brazil; Instituto de Neurociências e Comportamento (INeC), Ribeirão Preto, SP, Brazil.
authors: F M C V
authors: FM
authors: Reis
authors: Departamento de Fisiologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors: N
authors: N
authors: Pestana-Oliveira
authors: Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors: C M
authors: CM
authors: Leite
authors: Departamento de Ciências Fisiológicas, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors: F B
authors: FB
authors: Lima
authors: Laboratório de Neuropsicofarmacologia, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, 14049-901 Ribeirão Preto, SP, Brazil; Instituto de Neurociências e Comportamento (INeC), Ribeirão Preto, SP, Brazil.
authors: M L
authors: ML
authors: Brandão
authors: Instituto de Neurociências e Comportamento (INeC), Ribeirão Preto, SP, Brazil; Núcleo de Pesquisa em Neurobiologia das Emoções (NuPNE), Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors: F G
authors: FG
authors: Graeff
authors: Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors: C M
authors: CM
authors: Del-Ben
authors: Departamento de Morfologia, Fisiologia e Patologia Básica, Faculdade de Odontologia de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil. Electronic address: jaafranc@usp.br.
authors: J A
authors: JA
authors: Anselmo-Franci
mesh_terms: D000818:Animals; D001007:Anxiety / Q000097:blood / Q000139:chemically induced*; D003345:Corticosterone / Q000097:blood; D053138:Cyclohexenes / Q000633:toxicity*; D013196:Dihydrotestosterone / Q000097:blood; D004195:Disease Models, Animal; D004958:Estradiol / Q000097:blood; D030762:Estrous Cycle / Q000097:blood; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D018782:Maze Learning / Q000187:drug effects; D006080:Ovarian Follicle / Q000187:drug effects*; D047648:Perimenopause / Q000097:blood / Q000187:drug effects* / Q000523:psychology*; D016649:Primary Ovarian Insufficiency / Q000139:chemically induced; D011374:Progesterone / Q000097:blood; D051381:Rats; D013739:Testosterone / Q000097:blood; D014753:Vinyl Compounds / Q000633:toxicity*
chemical_list: D053138:Cyclohexenes; D014753:Vinyl Compounds; D013196:Dihydrotestosterone; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; C012606:4-vinyl-1-cyclohexene dioxide; D005640:Follicle Stimulating Hormone; D003345:Corticosterone
keywords: Anxiety; DHT; Estradiol; FSH; Follicular depletion; Glucocorticoids; Perimenopause; Progesterone; Testosterone