Behavioral characteristics of 5-HT2C receptor knockout mice: Locomotor activity, anxiety-, and fear memory-related behaviors
Behavioral characteristics of 5-HT2C receptor knockout mice: Locomotor activity, anxiety-, and fear memory-related behaviors
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DOI：
10.1016/j.bbr.2019.112394
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发表时间：
2020-02-03
影响因子：
2.7
通讯作者：
Yoshioka, Mitsuhiro
中科院分区：
文献类型：
--
作者：
Nebuka, Mao;Ohmura, Yu;Yoshioka, Mitsuhiro
药理学研究表明，血清素 5-HT2C 受体与运动活动、焦虑和恐惧记忆有关。然而，5-HT2C 受体敲除小鼠的运动活动和焦虑结果好坏参半，并且 5-HT2C 受体敲除对情境恐惧记忆的影响尚未得到解决。在本研究中，我们通过详细分析行为数据并检查 5-HT2C 受体敲除对情境恐惧记忆的影响来调和这些不一致的结果。我们证明，仅在测试的后期才观察到 5-HT2C 受体敲除小鼠的较高运动活性，这表明先前研究中使用总运动活性的分析将导致不同的结果。此外，通过详细分析小鼠行为，我们发现5-HT2C受体敲除小鼠在高架十字迷宫测试中表现出停留在中心区域的犹豫态度以及风险评估行为。然而，当使用缺乏中心区域的零迷宫测试时，5-HT2C 受体敲除小鼠在张开臂中花费的时间比野生型同窝小鼠更长。在情景恐惧调节测试中，与野生型同窝小鼠相比，5-HT2C 受体敲除小鼠表现出恐惧在会话内快速消退，但在会话间没有表现出恐惧消退。然而，这仍然是不确定的，因为5-HT2C受体敲除小鼠中，促进灭绝可能与较高的运动活性相混淆。总而言之，目前的结果为之前不一致的发现提供了合理的解释，并部分填补了药理学和遗传学发现之间的空白。
Pharmacological studies have suggested that the serotonin 5-HT2C receptor is involved in locomotor activity, anxiety, and fear memory. However, the results of locomotor activity and anxiety in 5-HT2C receptor knockout mice have been mixed, and the effects of 5-HT2C receptor knockout on contextual fear memory have not yet been addressed. In the present study, we reconcile these inconsistent results by analyzing behavioral data in detail and by examining the effects of 5-HT2C receptor knockout on contextual fear memory. We demonstrated that the higher locomotor activity in 5-HT2C receptor knockout mice was observed only in the late phase of the test, indicating that the analyses in the previous study using the total locomotor activity would lead to variable results. Moreover, by analyzing mouse behavior in detail, we found that 5-HT2C receptor knockout mice displayed a hesitating attitude by staying in the central area as well as risk assessment behavior in the elevated plusmaze test. However, the time spent in the open arms was longer in 5-HT2C receptor knockout mice than in wildtype littermates when a zero-maze test lacking the central area was used. In the contextual fear conditioning test, 5-HT2C receptor knockout mice showed rapid within-session extinction of fear, but not between-session extinction, compared with wild-type littermates. However, this remains inconclusive because the facilitation of extinction might be confounded with higher locomotor activity in 5-HT2C receptor knockout mice. Taken together, the present results provide reasonable explanations about previous inconsistent findings and partially filled the gaps between pharmacological and genetic findings.