PMID- 27343386 OWN - NLM STAT- MEDLINE DCOM- 20170619 LR - 20181113 IS - 1873-7064 (Electronic) IS - 0028-3908 (Print) IS - 0028-3908 (Linking) VI - 109 DP - 2016 Oct TI - Prediction of individual differences in fear response by novelty seeking, and disruption of contextual fear memory reconsolidation by ketamine. PG - 293-305 LID - S0028-3908(16)30275-1 [pii] LID - 10.1016/j.neuropharm.2016.06.022 [doi] AB - 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. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Duclot, Florian AU - Duclot F AD - Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, United States; Program in Neuroscience, Florida State University, Tallahassee, FL 32306, United States. FAU - Perez-Taboada, Iara AU - Perez-Taboada I AD - Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, United States; Program in Neuroscience, Florida State University, Tallahassee, FL 32306, United States. FAU - Wright, Katherine N AU - Wright KN AD - Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, United States; Program in Neuroscience, Florida State University, Tallahassee, FL 32306, United States. FAU - Kabbaj, Mohamed AU - Kabbaj M AD - Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, United States; Program in Neuroscience, Florida State University, Tallahassee, FL 32306, United States. Electronic address: mohamed.kabbaj@med.fsu.edu. LA - eng GR - R01 MH087583/MH/NIMH NIH HHS/United States GR - R01 MH099085/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20160622 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 690G0D6V8H (Ketamine) SB - IM MH - Animals MH - CA1 Region, Hippocampal/drug effects/physiology MH - Exploratory Behavior/*drug effects/physiology MH - Fear/*drug effects/physiology/*psychology MH - Forecasting MH - *Individuality MH - Ketamine/*pharmacology MH - Locomotion/drug effects/physiology MH - Male MH - Memory Consolidation/*drug effects/physiology MH - Rats MH - Rats, Sprague-Dawley PMC - PMC5017153 MID - NIHMS801060 OTO - NOTNLM OT - Fear conditioning OT - Fear extinction OT - Fear memory reconsolidation OT - Individual differences OT - Ketamine OT - Ketamine hydrochloride (PubChem CID: 3821) OT - Novelty seeking EDAT- 2016/06/28 06:00 MHDA- 2017/06/20 06:00 PMCR- 2017/10/01 CRDT- 2016/06/26 06:00 PHST- 2016/03/10 00:00 [received] PHST- 2016/05/23 00:00 [revised] PHST- 2016/06/21 00:00 [accepted] PHST- 2016/06/26 06:00 [entrez] PHST- 2016/06/28 06:00 [pubmed] PHST- 2017/06/20 06:00 [medline] PHST- 2017/10/01 00:00 [pmc-release] AID - S0028-3908(16)30275-1 [pii] AID - 10.1016/j.neuropharm.2016.06.022 [doi] PST - ppublish SO - Neuropharmacology. 2016 Oct;109:293-305. doi: 10.1016/j.neuropharm.2016.06.022. Epub 2016 Jun 22.