Mineralocorticoid and glucocorticoid receptor antagonists in animal models of anxiety

The behavioral effects of intracerebroventricular (ICV) administration of a specific mineralocorticoid receptor (MR) antagonist [RU28318 (10-50 ng/2 mu l)], a glucocorticoid receptor (GR) antagonist [RU38486 (1-50 ng/2 mu l)], or both antagonists (50 ng/2 mu l), were studied in two different animal models of fear and anxiety in rats. In the defensive burying paradigm simultaneous blockade of MR and GR increased immobility behavior, whereas a small decrease in defensive burying was seen. In the fear-potentiated startle test concurrent MR and GR blockade led to an increase in fear-potentiated startle at the highest loudness level (105 dB). In both tests the antagonists were not effective when given separately. The findings are discussed in terms of the involvement of CR and MR in neural mechanisms of fear and anxiety.