title: Rapid Activation of Glucocorticoid Receptors in the Prefrontal Cortex Mediates the Expression of Contextual Conditioned Fear in Rats.
abstract: The aim of the present study was to investigate the role of glucocorticoids in medial prefrontal cortex (mPFC) activity and the expression of contextual conditioned fear (freezing). Rats were pretreated with vehicle or metyrapone, a corticosterone synthesis blocker, and exposed to a context previously paired with footshocks. Freezing and Fos-protein expression in different mPFC regions were assessed. Exposure to the aversive context led to increased freezing and Fos expression in the prelimbic (PrL), anterior cingulate areas 1 and 2 (Cg1/Cg2). Pretreatment with metyrapone decreased freezing and Fos expression in these areas. Administration of spironolactone, an MR antagonist, in the PrL before the test decreased freezing. Pretreatment with RU38486, a glucocorticoid receptor (GR) antagonist, reduced this effect of spironolactone, suggesting that the effects of this MR antagonist may be attributable to a redirection of endogenous corticosterone actions to GRs. Consistent with this result, the decrease in freezing that was induced by intra-PrL injections of corticosterone was attenuated by pretreatment with RU38486 but not spironolactone. These findings indicate that corticosterone release during aversive conditioning influences mPFC activity and the retrieval of conditioned fear memory indicating the importance of balance between MR:GR-mediated effects in this brain region in this process.
authors.affiliation: Departamento de Psicologia, FFCLRP Instituto de Neurociências e Comportamento (INeC), Ribeirão Preto, SP, Brazil.
authors.forename: Fernando M C V
authors.initials: FM
authors.lastname: Reis
authors.affiliation: Instituto de Neurociências e Comportamento (INeC), Ribeirão Preto, SP, Brazil Departamento de Farmacologia, FMRP, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Rafael C
authors.initials: RC
authors.lastname: Almada
authors.affiliation: Instituto de Neurociências e Comportamento (INeC), Ribeirão Preto, SP, Brazil Departamento de Farmacologia, FMRP, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Manoela V
authors.initials: MV
authors.lastname: Fogaça
authors.affiliation: Departamento de Psicologia, FFCLRP Instituto de Neurociências e Comportamento (INeC), Ribeirão Preto, SP, Brazil.
authors.forename: Marcus L
authors.initials: ML
authors.lastname: Brandão
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000008:administration & dosage / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D006727:Hormone Antagonists / Q000494:pharmacology; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D015735:Mifepristone / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D006727:Hormone Antagonists; D016760:Proto-Oncogene Proteins c-fos; D011965:Receptors, Glucocorticoid; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D015735:Mifepristone; D003345:Corticosterone; D008797:Metyrapone
keywords: corticosterone; mineralocorticoid receptors; nongenomic effects; prelimbic cortex; spironolactone