Role of the 5-HT₂A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice.
Role of the 5-HT₂A receptor in the locomotor hyperactivity produced by phenylalkylamine hallucinogens in mice.
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DOI：
10.1016/j.neuropharm.2013.01.014
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发表时间：
2013-07
影响因子：
4.7
通讯作者：
Geyer MA
中科院分区：
文献类型：
--
作者：
Halberstadt AL;Powell SB;Geyer MA
5-HT2a受体介导5-羟色胺能致幻剂的作用，并可能在包括精神分裂症在内的某些精神疾病的病理生理学中发挥作用。鉴于这些发现，有必要建立动物模型来评估5-HT2A受体激活对行为的影响。我们以前的研究表明，苯烷胺致幻剂和5-HT2A/2C激动剂2，5-二甲氧基-4-碘苯丙胺(DOI)对C57BL/6J小鼠的运动活动产生剂量依赖性效应，在低到中剂量时增加活动，在高剂量时降低活动。DOI没有增加5-HT2A基因敲除小鼠的运动活性，这表明这种作用是5-HT2A受体激活的结果。在这里，我们使用行为模式监测器(BPM)在C57BL/6J小鼠身上测试了一系列苯烷胺迷幻剂，以确定这些化合物是否通过激活5-HT2A受体来增加运动活性。低剂量的甲斯卡林、2，5-二甲氧基-4-乙基苯丙胺(DOET)、2，5-二甲氧基-4-丙基苯丙胺(DOPR)、2，4，5-三甲氧基苯丙胺(TMA-2)和构象受限的苯乙胺(4-bromo-3，6-dimethoxybenzocyclobuten-1-yl)methylamine(TCB-2)可增加运动活动。相比之下，非致幻性苯烷基胺2，5-二甲氧基-4-叔丁基苯丙胺(DOTB)在所测试的任何剂量(0.1-10 mg/kg I.P.)下都不会改变运动能力。选择性5-HT2A拮抗剂M100907可阻断美斯卡林和TCB-2诱导的运动亢进。同样，美斯卡林和TCB-2没有增加5-HT2A基因敲除小鼠的运动活动。这些结果证实了苯烷胺迷幻剂增加了小鼠的运动活动，并证明这种作用是通过激活5-HT2a受体来实现的。因此，小鼠的运动性多动可用于评估苯烷基胺的5-HT2A激动剂活性和致幻剂样行为效应。这些研究为5-HT2A激活和幻觉发生之间的联系提供了额外的支持。
The 5-HT2A receptor mediates the effects of serotonergic hallucinogens and may play a role in the pathophysiology of certain psychiatric disorders, including schizophrenia. Given these findings, there is a need for animal models to assess the behavioral effects of 5-HT2A receptor activation. Our previous studies demonstrated that the phenylalkylamine hallucinogen and 5-HT2A/2C agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) produces dose-dependent effects on locomotor activity in C57BL/6J mice, increasing activity at low to moderate doses and reducing activity at high doses. DOI did not increase locomotor activity in 5-HT2A knockout mice, indicating the effect is a consequence of 5-HT2A receptor activation. Here, we tested a series of phenylalkylamine hallucinogens in C57BL/6J mice using the Behavioral Pattern Monitor (BPM) to determine whether these compounds increase locomotor activity by activating the 5-HT2A receptor. Low doses of mescaline, 2,5-dimethoxy-4-ethylamphetamine (DOET), 2,5-dimethoxy-4-propylamphetamine (DOPR), 2,4,5-trimethoxyamphetamine (TMA-2), and the conformationally restricted phenethylamine (4-bromo-3,6-dimethoxybenzocyclobuten-1-yl)methylamine (TCB-2) increased locomotor activity. By contrast, the non-hallucinogenic phenylalkylamine 2,5-dimethoxy-4-tert-butylamphetamine (DOTB) did not alter locomotor activity at any dose tested (0.1-10 mg/kg i.p.). The selective 5-HT2A antagonist M100907 blocked the locomotor hyperactivity induced by mescaline and TCB-2. Similarly, mescaline and TCB-2 did not increase locomotor activity in 5-HT2A knockout mice. These results confirm that phenylalkylamine hallucinogens increase locomotor activity in mice and demonstrate that this effect is mediated by 5-HT2A receptor activation. Thus, locomotor hyperactivity in mice can be used to assess phenylalkylamines for 5-HT2A agonist activity and hallucinogen-like behavioral effects. These studies provide additional support for the link between 5-HT2A activation and hallucinogenesis.
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直接和间接 5-HT 受体激动剂对 C57 BL/6J 小鼠的运动和垂直活动产生性别特异性影响。
影响因子：
3.6
作者：
Brookshire, Bethany R.;Jones, Sara R.
通讯作者：
Jones, Sara R.
影响因子：
3.4
作者：
Chen, Shih-Fen;Shen, Yu-Chih;Chen, Chia-Hsiang
通讯作者：
Chen, Chia-Hsiang
影响因子：
3.6
作者：
Berg, KA;Maayani, S;Clarke, WP
通讯作者：
Clarke, WP
影响因子：
3.5
作者：
Kishi, Taro;Yoshimura, Reiji;Iwata, Nakao
通讯作者：
Iwata, Nakao
影响因子：
7.3
作者：
Monte, AP;Waldman, SR;Nichols, DE
通讯作者：
Nichols, DE