A comparative study of the effects of selective and non-selective 5-HT2 receptor subtype antagonists in rat and mouse models of anxiety
A comparative study of the effects of selective and non-selective 5-HT2 receptor subtype antagonists in rat and mouse models of anxiety
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DOI：
10.1016/s0028-3908(97)00034-8
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发表时间：
1997-06-01
影响因子：
4.7
通讯作者：
Sanger, DJ
中科院分区：
文献类型：
--
作者：
Griebel, G;Perrault, G;Sanger, DJ
尽管有一些证据表明作用于 5-HT2 受体的化合物显示出抗焦虑活性，但人们对不同 5-HT2 受体亚型在调节焦虑相关反应中的具体参与知之甚少。在本研究中，研究了米安舍林（一种非选择性 5-HT2 受体拮抗剂）、MDL 100,907（一种选择性 5-HT2A 受体拮抗剂）和 SE 206553（一种选择性 5-HT2B/2C 受体拮抗剂）对两只大鼠（沃格尔饮酒冲突和高架十字迷宫测试）和两只小鼠（即小鼠防御测试电池 (MDTB) 和光/暗选择测试）的行为影响。焦虑模型。地西泮用作阳性对照。在 Vogel 饮酒测试中，米安舍林 (10 mg/kg) 和 SB 206553 (3-30 mg/kg)，而非 MDL 100,907，增加了惩罚反应。类似地，米安色林 (1 mg/kg) 和 SB 206553 (3-10 mg/kg)，但不是 MDL 100,907，增加了进入高架十字迷宫开放臂的次数。这些作用与米安舍林和 SE 206553 的抗焦虑样作用一致，尽管这两种化合物的作用幅度小于地西泮。此外，在MDTB中，5-HT2拮抗剂并没有明显影响暴露于大鼠刺激的小鼠的防御反应，并且它们未能逆转明/暗选择测试中对照明盒的回避。这些结果表明这些化合物对小鼠缺乏抗焦虑样作用。这些行为特征表明，阻断 5-HT2A 受体可能不会减少焦虑，并证明 5-HT2B 和/或 5-HT2C 受体亚型可能主要参与米安舍林和 SE 206553 在大鼠中的抗焦虑样作用。 (C) 1997 爱思唯尔科学有限公司。
Although there is some evidence that compounds acting at 5-HT2 receptors show anxiolytic activity, little is known about the specific involvement of the different 5-HT2 receptor subtypes in the modulation of anxiety-related responses. In the present study, the behavioural effects of mianserin, a nonselective 5-HT2 receptor antagonist, MDL 100,907, a selective 5-HT2A receptor antagonist, and SE 206553, a selective 5-HT2B/2C receptor antagonist, were investigated in two rat (the Vogel drinking conflict and the elevated plus-maze tests) and two mouse (i.e. the mouse defense test battery (MDTB) and the light/dark choice test) models of anxiety. Diazepam was used as a positive control. In the Vogel drinking test, mianserin (10 mg/kg) and SB 206553 (3-30 mg/kg), but not MDL 100,907, increased punished responding. Similarly, mianserin (1 mg/kg) and SB 206553 (3-10 mg/kg), but not MDL 100,907, increased entries into the open arms of the elevated plus-maze. These effects are consistent with anxiolytic-like actions of mianserin and SE 206553, although the magnitude of the effects of these two compounds was less than those of diazepam. In addition, in the MDTB, the 5-HT2 antagonists did not clearly affect the defensive reactions of mice exposed to a rat stimulus and they failed to reverse the avoidance of the illuminated box in the light/dark choice test. These results indicate a lack of anxiolytic-like action of the compounds in mice. These behavioural profiles suggest that blockade of the 5-HT2A receptor may not reduce anxiety and demonstrate that 5-HT2B and/or 5-HT2C receptor subtypes may be primarily involved in the anxiolytic-like effects of mianserin and SE 206553 in rats. (C) 1997 Elsevier Science Ltd.