Glucocorticoid and Mineralocorticoid Receptors Are Involved in the Facilitation of Anxiety-Like Response Induced by Restraint

Abstract

In previous studies, we have shown that male Wistar rats exposed to a single inescapable stressor session (15 min restraint) exhibited 24 h later an anxiogenic-like behavior in the elevated plus-maze (EPM), which was reversed by inhibition of corticosterone (CS) synthesis with metyrapone (75 mg/kg i.p.) 3 h before stress. Since CS binds to two central corticosteroid receptors, the mineralocorticoid (MR) and the glucocorticoid (GR) receptors, involvement of MR and GR in the modulation of anxiogenic responses was assessed in the EPM. Administration of the GR agonist dexamethasone (Dex, 1.25 µg/kg s.c.) to metyrapone-pretreated rats 1 h before restraint restored the anxiogenic-like response induced by the stressor. Removal of the adrenals also inhibited the anxiogenic-like effect, which was restored by either Dex (1.25 µg/kg s.c.), the MR agonist deoxycorticosterone (0.8 mg/kg s.c.) or CS, the common endogenous agonist of MR and GR (5 mg/kg s.c.) administered 1 h before stress. Intracerebroventricular infusion to intact animals 15 min before restraint of either a selective GR antagonist (A-GR, RU 38486, 100 ng/2 µl), a selective MR antagonist (A-MR, RU 28318, 100 ng/2 µl) or a combination of A-GR and A-MR (100 ng of each one/2 µl), abolished the stress-induced anxiogenic-like effect. The present findings indicate that both MR and GR are involved in the long-term CS modulation of the anxiety response induced by restraint. Both receptors mediate CS effects in an independent manner.

Corticosterone Synthesis Inhibitor Metyrapone Preserves Changes in Maternal Behavior and Neuroendocrine Responses during Immunological Challenge in Lactating Rats

“…These behavioral changes that occur during exposure to stress seem to reflect a decrease in anxiety. Other studies show that administration of metyrapone 3 h before exposure to restraint stress increases the spent time in the open arms during testing in an ETM [44,76]. Moreover, it has been shown that after administration of metyrapone, there are increases in the levels of 11-deoxycortisol and deoxycorticosterone [48], both of which are precursors for the synthesis of corticosterone.…”

Ethyl-eicosapentaenoic acid ingestion prevents corticosterone-mediated memory impairment induced by central administration of interleukin-1β in rats

“…The final concentration of ethanol was less than 1%. 22 Rats were gently held in a soft cotton towel every day for 2 weeks before the injection. On the injection day, IL-1b, RU486 or saline were taken into an injection needle (4.2 mm length) that was connected to a PE 50 polyethylene tube.…”

Biphasic Effects of Adrenal Steroids on Learned Helplessness Behavior Induced by Inescapable Shock

“…Adrenal steroids play an important role in regulating both learned and unlearned fear and anxiety (Korte 2001;Calvo et al, 1998;Calvo and Volosin, 2001) and alterations in the balance between Type I or mineralocorticoid receptors (MR) and Type II or glucocorticoid receptors (GR) in the brain appear to play a role in these behaviors as well as in the etiology of depression and anxiety (de Kloet et al, 1988;Korte, 2001). MR and GR are expressed throughout the central nervous system, with GR showing a more widespread distribution and MR showing a discrete localization, such as in neurons of the hippocampus, regions of the amygdala, and brain stem (Ahima and Harlan, 1990;Ahima et al, 1991).…”