A discriminative stimulus produced by 1-(3-chlorophenyl)-piperazine (mCPP) as a putative animal model of anxiety.
A discriminative stimulus produced by 1-(3-chlorophenyl)-piperazine (mCPP) as a putative animal model of anxiety.
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1-(3-氯苯基)-哌嗪 (mCPP) 产生的辨别刺激作为假定的焦虑动物模型。
DOI：
10.1016/s0278-5846(98)00024-4
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发表时间：
1998
影响因子：
5.6
通讯作者：
Lal,H
中科院分区：
文献类型：
--
作者：
Wallis,CJ;Lal,H
1. 本研究比较了用作焦虑动物模型的两种行为范式中对血清素 (SHT) 激动剂和戊四氮 (PTZ) 的行为反应。比较了 PTZ 和 mCPP 在高架十字迷宫中的行为效果以及它们产生的内感受辨别刺激。 2. 2. PTZ 是一种已知的致焦虑药物。选择 mCPP 的辨别刺激进行比较是因为该药物在人类受试者中产生“焦虑”，在大鼠中产生“类焦虑”行为，并且是 5HT 1B 2C 受体的强效激动剂和 5HT 2A 受体的部分激动剂。 3. 3. 在训练区分 mCPP（1.4 mg/kg，训练剂量）和盐水的大鼠中，PTZ 替代了 mCPP，表明 mCPP 刺激具有“类似焦虑”的特性。 mCPP 刺激被 5HT sol2A 2C 拮抗剂美西麦角以剂量相关的方式阻断，但抗焦虑药地西泮则不阻断。 TFMPP（5HT 激动剂）和 DOI（5HT 2A 2C 激动剂）替代了 mCPP，但 1-NP（5HT 1 激动剂和 5HT 2C 2A 拮抗剂）没有替代。 4. 4. 在经过训练区分 PTZ (16 mg/kg) 和盐水的动物中，mCPP 和 DOI 替代 PTZ，而 TFMPP 和 1-NP 则不能。 5. 5. 在高架十字迷宫中，mCPP、DOI 和 PTZ 减少了花在张开臂上的时间，但 TFMPP 或 1-NP 没有显着的剂量效应。 6. 6. 美西麦角阻断了 EPM 中的“类焦虑”行为。 7. 7. 这些数据表明，mCPP 产生的区别性刺激是基于其对 5HT 受体的选择性作用，它们在行为药理学中的应用可能为研究基于 5HT 的抗焦虑和抗焦虑药物的药理学提供另一种工具。
1. This study compares behavioral responses to serotonergic (SHT) agonists and pentylenetetrazol (PTZ) in two behavioral paradigms used as animal models of anxiety. PTZ and mCPP were compared for behavioral effects in elevated plus-maze and interoceptive discriminative stimuli they produce. 2. 2. PTZ is a known anxiogenic drug. The discriminative stimuli of mCPP were selected for comparison because this drug produces “anxiety” in human subjects and “anxiety-like” behaviors in rats, and is a potent agonist at 5HT 1B 2C receptors and a partial agonist at 5HT 2A receptors. 3. 3. In rats trained to discriminate mCPP (1.4 mg/kg, training dose) from saline, PTZ substituted for the mCPP suggesting the “anxiety-like” properties of the mCPP stimulus. The mCPP stimulus was blocked in a dose-related manner by methysergide, a 5HT sol2A 2C antagonist but not by the anxiolytic diazepam. TFMPP (a 5HT agonist) and DOI (a 5HT 2A 2C agonist) substituted for mCPP, but 1-NP (a 5 HT 1 agonist and 5HT 2C 2A antagonist) did not. 4. 4. In animals trained to discriminate PTZ (16 mg/kg) from saline, mCPP and DOI substituted for PTZ, while TFMPP and 1-NP do not. 5. 5. In the elevated plus maze, time spent on the open arms was reduced by mCPP, DOI and PTZ but there was no significant dose effect of TFMPP, or 1-NP. 6. 6. Methysergide blocked the “anxiety-like” behavior in the EPM. 7. 7. These data suggest that the discriminative stimuli produced by mCPP are based upon its selective actions on 5HT receptors and their use in behavioral pharmacology may offer another tool in studying pharmacology of 5HT based anxiogenic and anxiolytic drugs.