Interaction between glucocorticoids and the glutamatergic system in the medial prefrontal cortex on the expression of contextual conditioned fear

Abstract

Recently it has been given emphasis on role of the medial prefrontal cortex (mPFC) in processes related to aversive conditioning. The specific roles regarding emotional behavior and control of the autonomic nervous system seem to be associated with particular subregions of the mPFC. The activation of mineralocorticoid receptor (MR) and glucocorticoid (GR) in mPFC seems to be involved in situations of acute stress and Pavlovian conditioning. Thus, the aim of this project is to investigate through behavioral, immunohistochemical and pharmacological approaches, the role of different sub-areas that comprise the mPFC, pre-limbic (PrL), infra-limbic (IL) cortices and anterior cingulate area 1 and 2 (Cg1 and Cg2), in the expression of contextual conditioned fear responses. In a first experiment, before re-exposure of rats to a context previously paired with foot shocks, these animals will be treated with the corticosterone synthesis inhibitor, metyrapone, for further evaluation of the freezing response and expression of Fos protein in neurons of mPFC. Later, the roles of mineralocorticoid (MR) and glucocorticoid (GR) receptors in mPFC in the expression of conditioned fear will be evaluated through the locally infusion of agonists and antagonists of these receptors into the different sub regions of the mPFC. In a third experiment, the role of the glutamatergic system in the behavioral effects induced by corticosterone in mPFC will be investigated by combined local injection of a NMDA receptor antagonist and corticosterone on the freezing response. The results from this study will advance the understanding of the mechanisms underlying the cortical influence over defensive behavior induced by Pavlovian conditioning.