Activation of 5-HT1 receptor in lateral habenula impaired contextual fear memory and hippocampal LTP in rat
Activation of 5-HT1 receptor in lateral habenula impaired contextual fear memory and hippocampal LTP in rat
复制标题
外侧缰核 5-HT1 受体的激活损害大鼠情境恐惧记忆和海马 LTP
DOI：
10.1016/j.neulet.2021.136305
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发表时间：
2022-01-07
影响因子：
2.5
通讯作者：
Zhang，Jichuan
中科院分区：
文献类型：
--
作者：
Gu，Jingsheng;Hou，Zhijie;Zhang，Jichuan
5-羟色胺（5-hydroxytraptamine，5-HT）是一种神经递质，在情绪和动机中起重要作用。5-HT的作用在不同的核和受体亚型中各不相同。外侧缰核（Lateral habenula，LHb）位于脑内，与中缝核相连，在情绪和抑郁中起重要作用。本研究旨在探讨LHb内5-HT 1受体在恐惧学习中的作用。在恐惧条件反射前15 min或恐惧条件反射后即刻，将5-HT 1受体激动剂5-羧酰胺色胺马来酸盐（5-CT）注入大鼠双侧LHb（1 μg/μl，1 μl/侧）。结果发现，LHb中5-HT 1受体的激活可抑制大鼠恐惧记忆的获得，但不影响其巩固，并伴有海马长时程增强（LTP）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR）亚单位1（GluA 1）丝氨酸845位点磷酸化水平的降低。此外，5-CT还能减少高架十字迷宫中大鼠在旷场中心区的时间和在旷臂的时间。结果提示，激活LHb 5-HT 1受体可损害大鼠海马依赖性恐惧记忆的获得，增加焦虑样行为。
Serotonin (5-hydroxytraptamine, 5-HT) is a neurotransmitter plays important roles in emotion and motivation. The action of 5-HT varies across nucleus and the receptor sub-types. Lateral habenula (LHb) in a brain area reciprocally connects with raphe nucleus and plays important roles in emotion and depression. In this study, we aimed to study the role of 5-HT1receptor in LHb on fear learning. 15 min before or immediate after the fear conditioning, 5-Carboxyamidotrypamine maleate salt (5-CT), an agonist of 5-HT1receptor, was bilaterally delivered into LHb (1 μg/μl, 1 μl/side) in rats. We found that activation of 5-HT1receptor in LHb impaired the acquisition but not consolidation of fear memory in rats, which was accompanied by impaired long-term potentiation (LTP) and decreased phosphorylation of α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor (AMPAR) subunit 1 (GluA1) at the Ser845 site in hippocampus. In addition, 5-CT decreased the time spent in center area of the open field and time spent in open arm in elevated plus maze. These results suggest that activation of 5-HT1receptor in LHb impaired acquisition of hippocampal dependent fear memory and increased anxiety- like behavior in rats.