Impulsive action induced by amphetamine, cocaine and MK801 is reduced by 5-HT2C receptor stimulation and 5-HT2A receptor blockade
Impulsive action induced by amphetamine, cocaine and MK801 is reduced by 5-HT2C receptor stimulation and 5-HT2A receptor blockade
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DOI：
10.1016/j.neuropharm.2011.02.025
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发表时间：
2011-09-01
影响因子：
4.7
通讯作者：
Higgins, Guy A.
中科院分区：
文献类型：
--
作者：
Fletcher, Paul J.;Rizos, Zoe;Higgins, Guy A.
先前的研究表明，5-HT 2C受体激动剂和5-HT 2A受体拮抗剂减少冲动行为，以及精神兴奋剂的运动刺激作用。由于精神兴奋剂也增加冲动行为，我们研究了5-HT 2C受体激动剂Ro 60 -0175和5-HT 2A受体拮抗剂M100907对苯丙胺、可卡因和NMDA受体拮抗剂MK 801（地佐环平）诱导的冲动行为的影响。在成年雄性Long-Evans大鼠中，在5-选择系列反应时间（5-CSRT）测试中测量冲动行为作为过早反应。最初，我们确定安非他明（0.3 mg/kg）、可卡因（15 mg/kg）和MK 801（0.03 mg/kg）诱导的过早反应率相当，每次约为50-70，而基线条件下为10-15。然后将每种药物及其溶媒与Ro 60 -0175（0.1和0.6 mg/kg）或其溶媒或M100907（0.5 mg/kg）或其溶媒联合检测。在0.1 mg/kg Ro 60 -0175下，不会改变苯丙胺、可卡因或MK 801的作用。相比之下，0.6 mg/kg剂量减少了苯丙胺、可卡因和MK 801诱导的过早反应。M100907还减少了所有这三种药物诱导的过早反应。一般而言，Ro 60 -0175或M100907单独给药不会持续改变5-CSRT试验中任务表现的任何其他方面，包括完成的试验数量和应答准确性。这些数据表明，5-HT 2C受体的激活和5-HT 2A受体的阻断对冲动行为的测量具有看似相似的功能效应。(C)2011爱思唯尔有限公司版权所有。
Previous work has shown that 5-HT2C receptor agonists and 5-HT2A receptor antagonists reduce impulsive action, as well as the locomotor stimulant effect of psychomotor stimulants. Since psychomotor stimulants also increase impulsive action we examined the effects of the 5-HT2C receptor agonist Ro60-0175, and the 5-HT2A receptor antagonist M100907 on impulsive action induced by amphetamine, cocaine and the NMDA receptor antagonist MK801 (dizocilpine). Impulsive action was measured in adult male Long-Evans rats as premature responding in the 5-choice serial reaction time (5-CSRT) test. Initially, we determined that amphetamine (0.3 mg/kg), cocaine (15 mg/kg) and MK801 (0.03 mg/kg) induced comparable premature response rates of approximately 50-70 per session, compared to 10-15 responses under baseline conditions. Each drug and its vehicle were then tested in combination with Ro60-0175 (0.1 and 0.6 mg/kg) or its vehicle, or M100907 (0.5 mg/kg) or its vehicle. At 0.1 mg/kg Ro60-0175 did not modify the effects of amphetamine, cocaine or MK801. In contrast, the 0.6 mg/kg dose reduced premature responses induced by amphetamine, cocaine and MK801. M100907 also reduced premature responding induced by all three of these drugs. In general, treatment with Ro60-0175 or M100907 by itself did not consistently alter any of the other aspects of task performance in the 5-CSRT test including number of trials completed, and accuracy of responding. These data show that activation of 5-HT2C receptors and blockade of 5-HT2A receptors have seemingly similar functional effects on a measure of impulsive action.This article is part of a Special Issue entitled 'Serotonin: The New Wave'. (C) 2011 Elsevier Ltd. All rights reserved.