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Prediction of individual differences in fear response by novelty seeking, and disruption of contextual fear memory reconsolidation by ketamine.

Authors :
Duclot F
Perez-Taboada I
Wright KN
Kabbaj M
Source :
Neuropharmacology [Neuropharmacology] 2016 Oct; Vol. 109, pp. 293-305. Date of Electronic Publication: 2016 Jun 22.
Publication Year :
2016

Abstract

Only a portion of the population exposed to trauma will develop persistent emotional alterations characteristic of posttraumatic stress disorder (PTSD), which illustrates the necessity for identifying vulnerability factors and novel pharmacotherapeutic alternatives. Interestingly, clinical evidence suggests that novelty seeking is a good predictor for vulnerability to the development of excessive and persistent fear. Here, we first tested this hypothesis by analyzing contextual and cued fear responses of rats selected for their high (high responders, HR) or low (low responders, LR) exploration of a novel environment, indicator of novelty seeking. While HR and LR rats exhibited similar sensitivity to the shock and cued fear memory retention, fewer extinction sessions were required in HR than LR animals to reach extinction, indicating faster contextual and cued memory extinction. In a second part, we found an effective disruption of contextual fear reconsolidation by the N-methyl-d-aspartate receptor antagonist ketamine, associated with a down-regulation of early growth response 1 (Egr1) in the hippocampal CA1 area, and up-regulation of brain-derived neurotrophic factor (Bdnf) mRNA levels in the prelimbic and infralimbic cortices. Altogether, these data demonstrate a link between novelty seeking and conditioned fear extinction, and highlight a promising novel role of ketamine in affecting established fear memory.<br /> (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Details

Language :
English
ISSN :
1873-7064
Volume :
109
Database :
MEDLINE
Journal :
Neuropharmacology
Publication Type :
Academic Journal
Accession number :
27343386
Full Text :
https://doi.org/10.1016/j.neuropharm.2016.06.022