Poster Presentation The International Congress of Neuroendocrinology 2014

Glucocorticoid receptors mediate the rapid effects of intra-prelimbic prefrontal cortex injections of mineralocorticoid receptor antagonist and corticosterone on the expression of contextual conditioned fear in rats (#143)

Fernando MCV Reis 1 2 3 , Rafael C Almada 2 3 4 , Manoela V Fogaca 2 3 4 , Marcus L Brandão 1 2 3
  1. Psychology Department, FFCLRP, Ribeirão Preto
  2. Instituto de Neurociêncas e Comportamento - INeC, Ribeirão Preto
  3. University of São Paulo, Ribeirão Preto, SP, Brazil
  4. Pharmacology Department, FMRP, Ribeirão Preto

Abnormal medial prefrontal cortex (mPFC) activity has been implicated in depression, schizophrenia and other psychiatric disorders such as anxiety. Often, subjects with mPFC deficits display an inadequate regulation of emotional behaviors. Neuroendocrine and neuroanatomical studies have identified this region as a critical site for glucocorticoids actions in cognitive processes and termination of stress response. Although it is known that stress and acute changes on circulating corticosterone concentrations can rapidly influence memory and emotional behaviors through different activation of mineralocorticoid (MR) or glucocorticoid receptors (GR), the role of these receptors and the effects of glucocorticoids in the mPFC on the expression of conditioned fear remain to be elucidated. The present study investigated the administration of MR/GR antagonists in the prelimbic cortex (PrL) on freezing response of rats subjected to contextual fear conditioning. Additionally, the effects of corticosterone and combined administrations with MR and GR antagonists on freezing response were also evaluated. Wistar male rats received vehicle or different doses of MR/GR antagonists bilaterally into the PrL and were exposed to a context previously paired with footshocks. The results showed that administration of the MR antagonist reduced freezing expression while the GR antagonist produced no effects. Previous administration of GR antagonist into the PrL abolished the anxiolytic effects induced by MR antagonist in this region. Additionally, corticosterone administration in the PrL reduced the expression of conditioned fear, an effect abolished by previous GR antagonist administration. These findings suggest that the modulation of conditioned fear in the PrL is partly influenced by an interaction between mechanisms mediated by MR/GR receptors so that the anxiolytic effects produced by MR antagonism and corticosterone administration in this region may be due to an increased activation of GR and recruitment of the underlying mechanisms involved in the non-genomic effects mediated by GR activation. Financial support: FAPESP.