5-羟色胺是一种传递神经信号的物质，最新研究发现无法产生神经递质5-羟色胺的小鼠的焦虑程度较正常小鼠更低，但是保持恐惧记忆的时间更长。5-羟色胺是与一大批行为有关的重要的信号传导分子，但是和抑郁、焦虑以及创伤后应激障碍（PSTD）特别有关，所有这些都常常与学习和记忆困难有联系。中科院神经所丁玉强及其同事此前开发了一种遗传方法，用于从小鼠的脑中移除制造5-羟色胺的神经元，同时完整地保留其它神经元——其中许多拥有5-羟色胺的受体。
研究人员通过比较缺乏5-羟色胺的小鼠和对照组的小鼠，实验把小鼠置于被设计用于引发焦虑或恐惧的环境中。缺乏5-羟色胺的小鼠在一个高架迷宫的开口部分游荡的时候比对照组小鼠更加放松，这提示它们焦虑程度更低。在小鼠被置于特制的笼子里接受脚部电击的实验中，缺乏5-羟色胺的小鼠似乎比对照组小鼠保持对这个笼子的不愉快的记忆时间更长，而且更不容易忘记被电击。这组科学家报告说，向缺乏5-羟色胺的小鼠脑中直接注射5-羟色胺似乎可以消除这种显示小鼠因为它们的经历而产生压力的行为。（生物谷Bioon.com）
生物谷推荐原始出处：
PNAS published ahead of print August 11, 2008, doi:10.1073/pnas.0801329105
Enhanced contextual fear memory in central serotonin-deficient mice
Jin-Xia Dai*,†, Hui-Li Han†,‡, Meng Tian‡, Jun Cao‡, Jian-Bo Xiu*, Ning-Ning Song*, Ying Huang*, Tian-Le Xu*, Yu-Qiang Ding*,§, and Lin Xu‡,§,¶
+Author Affiliations
*Institute of Neuroscience and State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China;
‡Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China; and
¶Mental Health Institute, Second Xiangya Hospital of Central South University, Changsha 410011, China
↵†J.-X.D and H.-L.H contributed equally to this work.
Edited by Tomas Hökfelt, Karolinska Institutet, Stockholm, Sweden, and approved June 6, 2008 (received for review February 12, 2008)
Abstract
Central serotonin (5-HT) dysregulation contributes to the susceptibility for mental disorders, including depression, anxiety, and posttraumatic stress disorder, and learning and memory deficits. We report that the formation of hippocampus-dependent spatial memory is compromised, but the acquisition and retrieval of contextual fear memory are enhanced, in central 5-HT-deficient mice. Genetic deletion of serotonin in the brain was achieved by inactivating Lmx1b selectively in the raphe nuclei of the brainstem, resulting in a near-complete loss of 5-HT throughout the brain. BIOONThese 5-HT-deficient mice exhibited no gross abnormality in brain structures and had normal locomotor activity. Spatial learning in the Morris water maze was unaffected, but the retrieval of spatial memory was impaired. In contrast, contextual fear learning and memory induced by foot-shock conditioning was markedly enhanced, but this enhancement could be prevented by intracerebroventricular administration of 5-HT. Foot shock impaired long-term potentiation and facilitated long-term depression in hippocampal slices in WT mice but had no effect in 5-HT-deficient mice. Furthermore, bath application of 5-HT in 5-HT-deficient mice restored foot shock-induced alterations of hippocampal synaptic plasticity. Thus, central 5-HT regulates hippocampus-dependent contextual fear memory, and 5-HT modulation of hippocampal synaptic plasticity may be the underlying mechanism. The enhanced fear memory in 5-HT-deficient mice supports the notion that 5-HT deficiency confers susceptibility to posttraumatic stress disorder in humans.
