Selective and nonselective serotonin antagonists block the aversive stimulus properties of MK212 and m-chlorophenylpiperazine (mCPP) in mice.
Selective and nonselective serotonin antagonists block the aversive stimulus properties of MK212 and m-chlorophenylpiperazine (mCPP) in mice.
复制标题
选择性和非选择性血清素拮抗剂可阻断 MK212 和间氯苯基哌嗪 (mCPP) 对小鼠的厌恶刺激特性。
DOI：
10.1016/j.neuropharm.2005.07.015
复制
发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Lefever,Timothy
中科院分区：
文献类型：
--
作者：
Walker,EllenA;Kohut,StephenJ;Hass,RichardW;BrownJr,EdwardK;Prabandham,Anupama;Lefever,Timothy
血清素 2C(5-HT2C) 受体与治疗抑郁和焦虑等情绪障碍有关。在本研究中，评估了两种 5-HT2C 激动剂 MK212 和 mCPP 在小鼠中产生条件性味觉厌恶的能力。在两天的训练中，Swiss-Webster 雄性小鼠（19-34 克）接受训练，将新溶液的味道与注射不同剂量的 MK212 或 mCPP 联系起来。在两个交替的训练日中，小鼠被训练将不同口味的溶液与注射盐水联系起来。为了进行测试，同时呈现两种调味溶液，并且避免使用 MK212 或 mCPP 配对溶液表明条件性味觉厌恶。对于与 1.0 或 10mg/kg MK212 或 mCPP 配对的溶液，观察到强烈的条件性味觉厌恶。非选择性血清素拮抗剂赛庚啶、溴LSD、麦角林、美西麦角和米安色林可阻断条件性味觉厌恶的获得。选择性5-HT2B/2Cantagonist SB206,553阻断MK212和mCPP诱导的条件性味觉厌恶，尽管选择性5-HT2B/2Cantagonist SB200,646仅阻断mCPP诱导的条件性味觉厌恶。在单瓶程序中，MK212、溴-LSD 和米安色林未能改变 LiCl 诱导的条件性味觉厌恶的获得率。总而言之，这些数据表明血清素激动剂 MK212 和 mCPP 产生条件性味觉厌恶，并且这些作用主要通过 5-HT2C 受体介导。
Serotonin2C(5-HT2C) receptors have been implicated to treat mood disorders such as depression and anxiety. In the present study, the capacities of two 5-HT2Cagonists, MK212 and mCPP, to produce conditioned taste aversions in mice were evaluated. On two training days, Swiss-Webster male mice (19–34g) were trained to associate the flavor of a novel solution with the injection of various doses of MK212 or mCPP. On two alternate training days, mice were trained to associate a different flavored solution with an injection of saline. For testing, both flavored solutions were presented simultaneously and an avoidance of the MK212 or mCPP-paired solution indicated conditioned taste aversion. Robust conditioned taste aversions were observed to solutions paired with 1.0 or 10mg/kg MK212 or mCPP. Acquisition of conditioned taste aversions was blocked by nonselective serotonin antagonists cyproheptadine, bromo-LSD, metergoline, methysergide and mianserin. Selective 5-HT2B/2Cantagonist SB206,553 blocked both MK212- and mCPP-induced conditioned taste aversion although selective 5-HT2B/2Cantagonist SB200,646 only blocked mCPP-induced conditioned taste aversion. In a single-bottle procedure, MK212, bromo-LSD, and mianserin failed to alter acquisition rate of a LiCl-induced conditioned taste aversion. Taken together, these data indicate that the serotonin agonists MK212 and mCPP produce conditioned taste aversion and that these effects are mediated predominantly through 5-HT2Creceptors.