RESUMO
Profiling the variability related to the estrous cycle is essential for assessing depressive-like behavior and screening drugs. This study compares circulating plasma corticosterone levels [CORT] and behavioral alterations in mice exposed to sucrose preference, forced swimming, and tail suspension tests (SPT, FST, and TST, respectively). While SPT exposure did not significantly alter [CORT], FST and TST showed notable changes. Mice in the TST exhibited increased movement and decreased immobility time compared to FST, suggesting a lower likelihood of depressive-like behavior in male mice. Notably, during the proestrus phase, female mice displayed the highest tendency for depressive-like behavior and elevated [CORT], but similar response to antidepressants (imipramine and fluoxetine). The inherent stress of the FST and TST tasks appears to influence [CORT] as well as depressant and antidepressant effects. These comparisons provide valuable insights for further behavioral phenotyping, model sensitivity assessment, and deepen our neurobiological understanding of depression in the context of drug screening.
Assuntos
Antidepressivos , Fluoxetina , Camundongos , Masculino , Feminino , Animais , Antidepressivos/farmacologia , Fluoxetina/farmacologia , Depressão/tratamento farmacológico , Imipramina/farmacologia , Comportamento Animal , Natação , Modelos Animais de Doenças , Corticosterona , Elevação dos Membros PosterioresRESUMO
The present study investigated the hormonal and neural responses to stress in a perimenopause animal model induced by 4-vinylcyclohexene diepoxide (VCD), which induces progressive follicular depletion in rodents, allowing studies on the transition to ovarian failure. Female rats, aged 28 days old, were s.c. injected for 15 consecutive days with corn oil or VCD. At 85 ± 5 days after the onset of treatment, the jugular vein was cannulated in the afternoon of metoestrus and in next morning (dioestrus) at 10.00 am, rats were subjected to 30 minutes of restraint stress. Blood samples were withdrawn before (-5 minutes), during (2, 5, 15 and 30 minutes) and after (45, 60 and 90 minutes) stress and plasma prolactin, progesterone and corticosterone levels were measured. Animals were perfused, brains processed for c-Fos/tyrosine hydroxylase (TH) in the locus coeruleus (LC) and c-Fos/corticotrophin-releasing factor (CRF) in the paraventricular nucleus (PVN). In unstressed rats the density of ß-endorphin fibres was assessed in LC and PVN. In VCD-treated rats, stress-induced prolactin peak was higher, basal and peak progesterone levels were lower, and both levels of corticosterone were similar to controls. However, the recovery period was longer for both adrenal hormones. In VCD-treated rats the number of c-Fos/TH and c-Fos/CRF-immunoreactive neurones was higher whereas the density of ß-endorphin fibres was lower in LC and PVN. We surmise that the hyperactivity of the LC and PVN neurones in VCD-treated rats may be a result of the lower progesterone levels that resulted in the decrease of ß-endorphin content in both nuclei, thus impairing the negative-feedback mechanism in the recovery period.