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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Olanzapine and risperidone disrupt conditioned avoidance responding by selectively weakening motivational salience of conditioned stimulus: further evidence.
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Olanzapine and risperidone disrupt conditioned avoidance responding by selectively weakening motivational salience of conditioned stimulus: further evidence.

机译：奥氮平和利培酮通过有选择地削弱条件刺激的动机显着性来破坏条件回避反应：进一步的证据。

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Suppression of conditioned avoidance response is a preclinical behavioral index of antipsychotic activity. Previous work shows that olanzapine and risperidone disrupt avoidance response elicited by a less salient conditioned stimulus (CS2) to a greater extent than avoidance elicited by a more salient stimulus (CS1), suggesting that antipsychotic drugs may have a weakening action on motivational salience of stimuli. In the present study, we further examined this mechanism of antipsychotic action, focusing on the possible impact of baseline difference of CS1 and CS2 response rates on the avoidance-disruptive effect of olanzapine and risperidone. Rats were first trained to acquire avoidance responding in a procedure in which the number of CS2 trials (i.e. 20) was twice the number of CS1 trials (i.e. 10), but the percentage of CS2-shock pairing was set at 25% lower (15 trials out of 20) than the percentage of CS1-shock pairing (20 trials out of 20). They were then tested daily under olanzapine (0.5 and 1.0 mg/kg, sc) or risperidone (0.33 and 1.0 mg/kg, sc) for 5 consecutive days. Repeated olanzapine and risperidone treatment dose-dependently disrupted avoidance responding to both CS1 and CS2. Both drugs at the high dose disrupted the CS2 avoidance to a greater extent than the CS1 avoidance. In the final challenge test, rats previously treated with olanzapine were tested under risperidone (0.33 mg/kg), whereas rats previously treated with risperidone were tested under olanzapine (0.5 mg/kg). Results show that rats previously treated with risperidone 1.0mg/kg group made significantly fewer avoidance responses than the vehicles under olanzapine at 0.5 mg/kg. These findings confirm that olanzapine and risperidone disrupt avoidance response primarily by selectively attenuating the motivational salience of the CS. The present study also suggests that there is a generality of antipsychotic drug experience that is mediated by a shared interoceptive drug state mechanism.
机译：有条件回避反应的抑制是抗精神病药活动的临床前行为指标。先前的工作表明，奥氮平和利培酮对显着条件刺激（CS2）引起的回避反应的干扰程度要比对更显着刺激（CS1）引起的回避更大程度的暗示，这表明抗精神病药可能对刺激性刺激性刺激作用减弱。 。在本研究中，我们进一步研究了这种抗精神病药物作用机制，重点研究了CS1和CS2反应率的基线差异对奥氮平和利培酮的避免-干扰作用的可能影响。首先训练大鼠获得规避反应的程序，其中CS2试验的次数（即20）是CS1试验的次数（即10）的两倍，但CS2休克配对的百分比设置为低25％（15）尝试CS20配对的百分比（20个实验中有20个）。然后每天在奥氮平（0.5和1.0 mg / kg，sc）或利培酮（0.33和1.0 mg / kg，sc）下每天连续5天进行测试。重复的奥氮平和利培酮治疗剂量依赖性地中断了对CS1和CS2的反应。两种药物都比CS1避免更大程度地破坏了CS2的避免。在最后的攻击试验中，先前用奥氮平治疗的大鼠在利培酮（0.33 mg / kg）下进行测试，而先前用利培酮治疗的大鼠在奥氮平（0.5 mg / kg）下进行测试。结果显示，先前使用利培酮1.0mg / kg组治疗的大鼠产生的回避反应明显少于在0.5mg / kg的奥氮平下使用的媒介物。这些发现证实，奥氮平和利培酮主要通过选择性地减弱CS的动机显着性来破坏回避反应。本研究还表明，抗精神病药的经验是普遍存在的，这是由一种共享的互感药状态机制介导的。

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