Evaluation of the motor initiation hypothesis of APD-induced conditioned avoidance decreases
Evaluation of the motor initiation hypothesis of APD-induced conditioned avoidance decreases
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DOI：
10.1016/j.pbb.2004.05.023
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发表时间：
2004-08-01
影响因子：
3.6
通讯作者：
Kapur, S
中科院分区：
文献类型：
--
作者：
Li, M;Parkes, J;Kapur, S
抗精神病药物(APD)选择性地破坏条件性回避反应(CAR)--这是它们与所有其他精神药物区别的一个特征。这一效应被认为反映了它们对运动启动的影响；然而，这一结论是值得怀疑的，因为它所依赖的大多数研究通常检查了雪崩治疗下的回避反应，并测试了锁前刺激和足部电击的动物。APDS的运动效应和足部电击的存在混淆了APD诱导的汽车效应。这项研究的目的是通过测试没有药物的动物和在灭绝条件下的动物来评估运动启动假说。在实验1中，我们在CAR的获取阶段给予氟哌啶醇、氯氮平或氯氮卓酮(一种抗焦虑药物)，但在2天后对动物进行测试。即使在没有药物和脚电击的情况下，警方引发的汽车中断也是存在的。在实验2中，我们首先训练大鼠达到学习标准，然后在药物或交通工具下对它们进行为期4天的汽车消退训练。在随后的CAR消退测试中，之前接受APDS治疗的大鼠仍然表现出明显较低的回避反应。在这两个实验中，氟哌啶醇和氯氮平的作用与氯氮卓酮不同。这些数据表明，apd诱导的CAR减少不能解释为APDS的无条件运动损伤效应，但可能反映了多巴胺阻断介导的激励动机的改变。(C)2004 Elsevier Inc.保留所有权利。
Antipsychotic drugs (APDs) selectively disrupt conditioned avoidance responding (CAR)-a feature that distinguishes them from all other psychotropics. It is thought that this effect reflects their effect on motor initiation; however, this conclusion is questionable because most studies it relies on have often examined avoidance responding under APD treatment, and tested animals with preshock stimuli followed by the footshock. APD-induced CAR effects are confounded by APDs' motor effects and by the presence of footshock. The objective of this study was to evaluate the motor initiation hypothesis by testing animals without drug and under extinction conditions. In Experiment 1, we administered haloperidol, clozapine or chlordiazepoxide (an anxiolytic as a pharmacological control) during the acquisition phase of CAR, but tested animals 2 days later. The APD-induced CAR disruption was present even in the absence of the drug and footshock. In Experiment 2, we first trained rats to a learning criterion, and then subjected them to 4 days of CAR extinction training under drug or vehicle. In the subsequent CAR extinction tests, the rats previously treated with APDs still showed significantly lower avoidance responses. In both experiments, the effects of haloperidol and clozapine were distinct from those of chlordiazepoxide. These data suggest that APD-induced CAR decreases cannot be explained as the unconditioned motor impairment effects of APDs, but probably reflect a dopamine-blockade-mediated change in incentive motivation. (C) 2004 Elsevier Inc. All rights reserved.