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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Disruption of conditioned reward association by typical and atypical antipsychotics.
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Disruption of conditioned reward association by typical and atypical antipsychotics.

机译：典型的和非典型的抗精神病药会破坏条件奖励协会。

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Antipsychotic drugs are broadly classified into typical and atypical compounds; they vary in their pharmacological profile however a common component is their antagonist effects at the D2 dopamine receptors (DRD2). Unfortunately, diminished DRD2 activation is generally thought to be associated with the severity of neuroleptic-induced anhedonia. The purpose of this study was to determine the effect of the atypical antipsychotic olanzapine and typical antipsychotic haloperidol in a paradigm that reflects the learned transfer of incentive motivational properties to previously neutral stimuli, namely autoshaping. In order to provide a dosing comparison to a therapeutically relevant endpoint, both drugs were tested against amphetamine-induced disruption of prepulse inhibition as well. In the autoshaping task, rats were exposed to repeated pairings of stimuli that were differentially predictive of reward delivery. Conditioned approach to the reward-predictive cue (sign-tracking) and to the reward (goal-tracking) increased during repeated pairings in the vehicle treated rats. Haloperidol and olanzapine completely abolished this behavior at relatively low doses (100microg/kg). This same dose was the threshold dose for each drug to antagonize the sensorimotor gating deficits produced by amphetamine. At lower doses (3-30microg/kg) both drugs produced a dose-dependent decrease in conditioned approach to the reward-predictive cue. There was no difference between drugs at this dose range which indicates that olanzapine disrupts autoshaping at a significantly lower proposed DRD2 receptor occupancy. Interestingly, neither drug disrupted conditioned approach to the reward at the same dose range that disrupted conditioned approach to the reward-predictive cue. Thus, haloperidol and olanzapine, at doses well below what is considered therapeutically relevant, disrupts the attribution of incentive motivational value to previously neutral cues. Drug effects on this dimension of reward processing are an important consideration in the development of future pharmacological treatments for schizophrenia.
机译：抗精神病药大致分为典型化合物和非典型化合物。它们的药理作用各不相同，但是常见的组成部分是它们对D2多巴胺受体（DRD2）的拮抗作用。不幸的是，DRD2激活减少通常被认为与精神安定剂引起的快感缺乏症的严重程度有关。这项研究的目的是确定一种典型的抗精神病药物奥氮平和典型的抗精神病药物氟哌啶醇的作用模式，该作用模式反映了学习型的动机动机特性向先前的中性刺激（即自塑）的转移。为了提供与治疗相关终点的剂量比较，还对两种药物都进行了抗苯丙胺诱导的前脉冲抑制破坏的测试。在自动塑形任务中，将大鼠暴露于重复配对的刺激下，这些刺激对以不同方式预测奖励的交付。在媒介物治疗的大鼠中反复配对期间，奖励预测提示（符号追踪）和奖励（目标追踪）的条件式处理增加了。氟哌啶醇和奥氮平以相对较低的剂量（100microg / kg）完全消除了这种行为。相同剂量是每种药物拮抗苯丙胺产生的感觉运动门控缺陷的阈值剂量。在较低剂量（3-30微克/千克）下，两种药物在奖励预测提示的条件处理中均产生剂量依赖性降低。在该剂量范围内的药物之间没有差异，这表明奥氮平以显着较低的拟议DRD2受体占有率破坏了自体成形。有趣的是，在破坏剂量预测性提示的条件剂量相同的剂量范围内，没有一种药物会破坏条件性的奖励方法。因此，氟哌啶醇和奥氮平的剂量远低于被认为与治疗相关的剂量，从而破坏了激励动机价值对先前中性线索的影响。在奖励治疗的这一维度上的药物作用是未来精​​神分裂症药理学发展的重要考虑因素。

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