Effects of corticosterone synthesis blockade on the Elevated Plus Maze test in females at different stages of the estrous cycle

Abstract

Corticosterone is a glucocorticoid hormone related to the expression of fear/anxiety responses in dangerous situations. Blocking its synthesis with the use of the drug metyrapone is capable of reducing unconditioned defensive responses in male rats. Recent studies have shown that, considering the estrous cycle, females sometimes exhibit different behaviors and responses than those observed in male rats. Therefore, the present study aims to expand knowledge about the involvement of corticosterone in the expression of unconditioned fear in males and females at different stages of the estrous cycle. We will evaluate the effects of metyrapone on the expression of defensive behaviors in the elevated plus maze (EPM) in males and females in proestrus/estrus and metestrus/diestrus, checking whether metyrapone is capable of altering defensive responses without affecting general exploratory behavior. For this, 108 Wistar rats, 72 females, and 36 males, weighing approximately 250 g will be used. Before the tests, there will be a habituation period of the animals to the laboratory, as well as the daily determination of the estrous cycle phase of the females. Then, on the day of the test, the control group animals will receive intraperitoneal administration of the vehicle, and the experimental group animals will receive metyrapone 30 or 60 mg/kg. Twenty minutes after administration, the animal will be placed in the EPM for behavioral evaluation for 5 minutes. After the EPM, rats will be evaluated during 5 min in the open field (OF). It is expected that blocking the synthesis of corticosterone through intraperitoneal administration of metyrapone will reduce the expression of defensive responses without affecting overall exploratory activity.