title: Prediction of individual differences in fear response by novelty seeking, and disruption of contextual fear memory reconsolidation by ketamine.
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.
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, United States; Program in Neuroscience, Florida State University, Tallahassee, FL 32306, United States.
authors.forename: Florian
authors.initials: F
authors.lastname: Duclot
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, United States; Program in Neuroscience, Florida State University, Tallahassee, FL 32306, United States.
authors.forename: Iara
authors.initials: I
authors.lastname: Perez-Taboada
authors.affiliation: Department of Biomedical Sciences, Florida State University, Tallahassee, FL 32306, United States; Program in Neuroscience, Florida State University, Tallahassee, FL 32306, United States.
authors.forename: Katherine N
authors.initials: KN
authors.lastname: Wright
authors.affiliation: 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.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Kabbaj
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology; D005106:Exploratory Behavior / Q000187:drug effects* / Q000502:physiology; D005239:Fear / Q000187:drug effects* / Q000502:physiology / Q000523:psychology*; D005544:Forecasting; D007206:Individuality; D007649:Ketamine / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D000069077:Memory Consolidation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007649:Ketamine
keywords: Fear conditioning; Fear extinction; Fear memory reconsolidation; Individual differences; Ketamine; Ketamine hydrochloride (PubChem CID: 3821); Novelty seeking