Study on the role of corticosteroids in the one-trial tolerance to the anxiolytic-like effects of Midazolam in mice exposed to the elevated plus maze

Abstract

The elevated plus-maze (EPM) is a widely used animal model for screening of new pharmacological agents to anxiety as well as for studies on the neurobiology of defensive behaviors. Interestingly, the anxiolytic-like effect of benzodiazepines, such as midazolam, is abolished in rats or mice previously tested in the EPM, a phenomenon described as one-trial tolerance (OTT). Previous studies have demonstrated that the learning from an initial experience in the EPM is involved in this process, suggesting that stress hormones would have a key role in the behavioral and cognitive changes between test and retest in the apparatus. The present project proposes to investigate whether corticosteroid receptors are involved in the development of OTT. For this, we will investigate (a) the effects of different doses of midazolam in a test and retest protocol using the EPM for the characterization of OTT, and (b) the effects of spironolactone, a mineralocorticoid antagonist, and mifepristone, a glucocorticoid antagonist, on the OTT to the anxiolytic-like effects of midazolam. (AU)