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Prediction of individual differences in fear response by novelty seeking, and disruption of contextual fear memory reconsolidation by ketamine.
- 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.)
- Subjects :
- Animals
CA1 Region, Hippocampal drug effects
CA1 Region, Hippocampal physiology
Exploratory Behavior physiology
Fear physiology
Forecasting
Locomotion drug effects
Locomotion physiology
Male
Memory Consolidation physiology
Rats
Rats, Sprague-Dawley
Exploratory Behavior drug effects
Fear drug effects
Fear psychology
Individuality
Ketamine pharmacology
Memory Consolidation drug effects
Subjects
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