title: Paradoxical mineralocorticoid receptor-mediated effect in fear memory encoding and expression of rats submitted to an olfactory fear conditioning task.
abstract: There is general agreement that the substantial modification in memory and motivational states exerted by corticosteroids after a traumatic experience is mediated in complementary manner by the mineralocorticoid (MR) and glucocorticoid (GR) receptors. Here we tested the hypothesis that pharmacological manipulation of MR activity would affect behavioral strategy and information storage in an olfactory fear conditioning (OFC) task. Male Wistar rats were submitted to the OFC with different training intensities. We observed that following high intensity OFC acquisition, a set of defensive coping strategies, which includes avoidance and risk assessment behaviors, was elicited when subjects were exposed to the conditioned stimulus (CS) 48 h later. In addition, following either OFC acquisition or retrieval (CS-I test) a profound corticosterone secretion was also detected. Systemic administration of the MR antagonist spironolactone altered the behavioral coping style irrespective the antagonist was administered 60 min prior to the acquisition or before the retrieval session. Surprisingly, the MR agonist fludrocortisone given 60 min prior to acquisition or retrieval of OFC had similar effects as the antagonist. In addition, post-training administration of fludrocortisone, following a weak training procedure, facilitated the consolidation of OFC. Fludrocortisone rather than spironolactone reduced serum corticosterone levels, suggesting that, at least in part, the effects of the MR agonist may derive from additional GR-mediated HPA-axis suppression. In conclusion, the present study suggests the involvement of the MR in the fine-tuning of behavioral adaptation necessary for optimal information storage and expression, as revealed by the marked alterations in the risk assessment behavior.
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Trindade, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Rimenez R
authors.initials: RR
authors.lastname: Souza
authors.affiliation: Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Silvia
authors.initials: S
authors.lastname: Dal Bó
authors.affiliation: Department of Medical Pharmacology, LACDR, Leiden University Medical Center, Leiden, The Netherlands; Department of Endocrinology and Metabolism, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: E Ronald
authors.initials: ER
authors.lastname: de Kloet
authors.affiliation: Swammerdam Institute for Life Sciences, SILS-CNS, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Melly S
authors.initials: MS
authors.lastname: Oitzl
authors.affiliation: Departamento de Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Trindade, 88040-900 Florianópolis, SC, Brazil. Electronic address: apcarobrez@gmail.com.
authors.forename: Antonio P
authors.initials: AP
authors.lastname: Carobrez
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D003345:Corticosterone / Q000097:blood; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D005438:Fludrocortisone / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D055696:Olfactory Perception / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000819:agonists* / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology
chemical_list: D000451:Mineralocorticoid Receptor Antagonists; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D005438:Fludrocortisone; D003345:Corticosterone
keywords: Coping strategy; Fear memory encoding; Mineralocorticoid receptor; Olfactory fear conditioning; Risk assessment behavior; Stress