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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Avoidance disruptive effect of clozapine and olanzapine is potentiated by increasing the test trials: Further test of the motivational salience hypothesis
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Avoidance disruptive effect of clozapine and olanzapine is potentiated by increasing the test trials: Further test of the motivational salience hypothesis

机译：通过增加试验试验，避免氯氮平和奥氮平的破坏性效果是增强的：进一步测试激励显着假设

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Antipsychotic drugs suppress animals' ability to avoid an aversive stimulus in the conditioned avoidance response model (CAR). This behavioral effect is thought to reflect antipsychotic activity and is suggested to be mediated by a drug's action in attenuating the motivational salience of a conditioned stimulus (CS). In the present study, we tested whether atypical antipsychotic drugs clozapine and olanzapine act through this behavioral mechanism by manipulating the number of avoidance test trials. We reasoned that more CS trials in the presence of clozapine or olanzapine would afford the drug more opportunities to decrease the motivational salience of the CS, thus avoidance decline would be greater with the increase of CS trials in each test session. In two separate experiments, adult male Sprague-Dawley rats were tested under clozapine (5.0 mg/kg, sc), olanzapine (0.5 mg/kg, sc) or vehicle (sterile water) for 6 consecutive days in three CS trial conditions (i.e. 3, 10, and 40 CS trials per session). Two days later, all rats were tested under the same 40-trial session after receiving clozapine (5.0 mg/kg, sc) or olanzapine (0.5 mg/kg, sc). Results show that repeated clozapine and olanzapine treatment persistently decreased avoidance response, and this effect was potentiated by the increase of number of CS trials in the test sessions, as the clozapine-treated or olanzapine-treated rats tested under the 40-trial or 10-trial condition had significantly lower avoidance and faster decline across-sessions than those tested under the 3-trial condition. This potentiated effect was not only seen in the total avoidance percentage, but also observed in the within-session decline pattern in the last three drug test sessions and in the final 40-trial test session. These findings suggest that the clinical efficacy of a drug can be enhanced by increasing the exposure of symptoms in the presence of the drug. ? 2012 Elsevier Inc. All rights reserved.
机译：抗精神病药物抑制动物在避免条件避免响应模型（汽车）中避免厌恶刺激的能力。认为这种行为效应是反映抗精神病药活动，并建议通过药物的作用来介导，以减轻条件刺激（CS）的动机显着性。在本研究中，我们通过操纵测试试验的数量来测试非典型抗精神病药物氯氮平和奥拉扎滨是否通过这种行为机制作用。我们推理在氯氮平或奥氮藻存在的情况下，更多的CS试验将提供更多的机会来降低CS的动机显着性，因此随着每个测试会议的Cs试验的增加，避免下降将会更大。在两个单独的实验中，在三个CS试验条件下连续6天在氯氮平（5.0mg / kg，sc），奥氮藻（0.5mg / kg，sc），奥氮藻（0.5mg / kg，sc）或载体（无菌水）下测试成年雄性Sprague-Dawley大鼠（即每次3,10和40 CS试验）。两天后，在接受氯氮平（5.0mg / kg，sc）或奥氮滨（0.5mg / kg，sc）后，所有大鼠都在相同的40试验中进行测试。结果表明，重复的氯氮平和奥氮平治疗持续降低避免响应，并且由于在40试验或10-试验下测试的氯氮平处理或奥烷曲线处理的大鼠的CS试验数量增加，这种效果具有增强。试验条件显着降低避免，比在3次试验条件下测试的速度更快。这种增强的效果不仅在避税的总避免百分比中看到，而且在最后三种药物测试会议和最终的40次试验课程中也观察到在会次内衰退模式中观察到。这些发现表明，通过增加药物存在下的症状暴露，可以提高药物的临床疗效。还2012年elsevier Inc.保留所有权利。

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