Prediction of individual differences in fear response by novelty seeking, and disruption of contextual fear memory reconsolidation by ketamine.
Prediction of individual differences in fear response by novelty seeking, and disruption of contextual fear memory reconsolidation by ketamine.
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DOI：
10.1016/j.neuropharm.2016.06.022
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发表时间：
2016-10
影响因子：
4.7
通讯作者：
Kabbaj M
中科院分区：
文献类型：
--
作者：
Duclot F;Perez-Taboada I;Wright KN;Kabbaj M
只有一部分暴露在创伤中的人群会出现创伤后应激障碍(PTSD)所特有的持续性情绪改变，这说明了确定脆弱因素和新的药物治疗替代方案的必要性。有趣的是，临床证据表明，寻求新奇事物可以很好地预测过度和持续恐惧的易感性。在这里，我们首先通过分析背景和线索恐惧反应来检验这一假设，这些大鼠被选为对新环境的高(高反应者，HR)或低(低反应者，LR)探索的大鼠，这是寻求新奇的指标。虽然HR和LR大鼠对休克和线索恐惧记忆保持表现出类似的敏感性，但HR大鼠比LR动物需要更少的消退时间才能达到消亡，这表明背景记忆和线索记忆消退更快。在第二部分中，我们发现N-甲基-D-天冬氨酸受体拮抗剂氯胺酮有效地破坏了背景恐惧的再巩固，与海马CA1区早期生长反应1(Egr1)的下调以及大脑前叶和边缘下皮质脑源性神经营养因子(BDNF)mRNA水平的上调有关。总而言之，这些数据证明了寻求新奇事物和消除条件性恐惧之间的联系，并突出了氯胺酮在影响既定恐惧记忆方面的一个有前景的新作用。
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.
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影响因子：
11
作者：
Chowdhury GM;Zhang J;Thomas M;Banasr M;Ma X;Pittman B;Bristow L;Schaeffer E;Duman RS;Rothman DL;Behar KL;Sanacora G
通讯作者：
Sanacora G
影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
3.7
作者：
Corlett PR;Cambridge V;Gardner JM;Piggot JS;Turner DC;Everitt JC;Arana FS;Morgan HL;Milton AL;Lee JL;Aitken MR;Dickinson A;Everitt BJ;Absalom AR;Adapa R;Subramanian N;Taylor JR;Krystal JH;Fletcher PC
通讯作者：
Fletcher PC
影响因子：
56.9
作者：
Eisenberg, M;Kobilo, T;Dudai, Y
通讯作者：
Dudai, Y
影响因子：
5.6
作者：
Browne CA;Lucki I
通讯作者：
Lucki I