Department of Biomedical Sciences, National Institute of Neuroscience, University of Cagliari, Via Ospedale 72, Cagliari, Italy.
Psychopharmacology (Berl). 2013 Feb;225(3):697-706. doi: 10.1007/s00213-012-2856-0. Epub 2012 Sep 8.
Sensitization of the incentive and dopamine (DA) stimulant properties of drug-conditioned stimuli (CSs) by repeated exposure to drugs of abuse has been assigned an important role in the genesis of drug addiction.
To test in rats if morphine-induced sensitization potentiates incentive and DA-releasing properties in the nucleus accumbens (NAc) shell and core elicited by presentation of a morphine-conditioned stimulus(CS) and if this property generalizes to a non-drug-(palatable food, Fonzies)-CS.
Controls and rats previously sensitized by morphine were trained via three daily sessions consisting of a 10-min presentation of CS (Fonzies filled box, FB) followed by s.c. saline and morphine (1 mg/kg) or by standard food and Fonzies. Rats were implanted with microdialysis probes and the next-day incentive reactions and NAc shell and core DA were monitored during CS presentation and subsequent morphine (1 mg/kg) administration or Fonzies feeding.
Morphine sensitization increased incentive and NAc shell and core DA responses to morphine-CS. Morphine conditioning per se increased incentive reactions and NAc shell but not core DA responses to FB presentation. Morphine sensitization potentiated incentive responses but did not affect NAc shell and core DA responses to Fonzies-CS. Fonzies conditioning increased incentive reactions and NAc core but not shell DA responses to FB presentation.
These observations confirm the prediction of the incentive sensitization theory in the case of drug-CS but not of non-drug-CS. NAc DA might be differentially involved in the expression of incentive sensitization of drug- and non-drug-CSs, thus providing a clue for the abnormal incentive properties of drug CSs.
反复暴露于滥用药物会使药物条件刺激（CS）的激励和多巴胺（DA）刺激特性敏感化，这在成瘾的发生中起重要作用。
在大鼠中测试，如果吗啡诱导的敏化增强了由吗啡条件刺激（CS）呈现引起的伏隔核（NAc）壳和核中的激励和 DA 释放特性，并且这种特性是否概括为非药物（美味食物，Fonzies）-CS。
对照组和先前通过吗啡敏化的大鼠通过三个每日训练课程进行训练，包括 10 分钟的 CS（装满 Fonzies 的盒子，FB）呈现，然后进行皮下盐水和吗啡（1mg/kg）或标准食物和 Fonzies 喂养。大鼠植入微透析探针，在 CS 呈现和随后的吗啡（1mg/kg）给药或 Fonzies 喂养期间监测激励反应和 NAc 壳和核 DA。
吗啡敏化增加了吗啡-CS 对激励和 NAc 壳和核 DA 的反应。吗啡条件本身增加了对 FB 呈现的激励反应和 NAc 壳，但不增加核心 DA 反应。吗啡敏化增强了对 Fonzies-CS 的激励反应，但不影响 NAc 壳和核 DA 反应。Fonzies 条件增加了对 FB 呈现的激励反应和 NAc 核心，但不增加壳 DA 反应。
这些观察结果证实了激励敏感化理论在药物 CS 情况下的预测，但不适用于非药物 CS。NAc DA 可能在药物和非药物 CS 的激励敏感化表达中差异参与，从而为药物 CS 的异常激励特性提供了线索。
