Background

The mechanisms through which drug-cue–induced negative affective states are involved in relapse have not been defined. We tested the hypothesis that in individuals having developed a dorsolateral striatum (DLS)–dependent cue-controlled cocaine-seeking habit, the loss of the opportunity to enact the drug-seeking response during abstinence results in an urge to act that exacerbates relapse severity mediated by negative urgency.

Methods

Eighty-seven male Sprague Dawley rats were trained to seek cocaine under the influence of the conditioned reinforcing properties of drug-paired cues or not. We investigated whether the tendency to relapse depended on the aversive state of withdrawal or instead on the loss of opportunity to perform the ingrained drug-seeking response after periods of abstinence. The striatal locus of control over cocaine seeking at baseline and relapse was investigated using in situ hybridization of the cellular activity marker C-fos and assessment of the sensitivity of instrumental drug seeking to dopamine receptor blockade in the dorsomedial striatum–dependent goal-directed and DLS-dependent habit systems.

Results

The development of a DLS-dependent cue-controlled cocaine-seeking habit prior to abstinence resulted in a marked increase in drug seeking at relapse, which was not motivated by a cocaine withdrawal state and was no longer dependent on the DLS habit system. Instead, it reflected the emergence of negative urgency caused by the prevention of the performance of the habit during abstinence and underpinned by transient engagement of the goal-directed system.

Conclusions

These results show that ingrained cue-controlled drug-seeking habits increase the pressure to relapse.

中文翻译：

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消极的紧迫感加剧了戒断后可卡因的复发

 背景

药物提示诱发的负面情感状态与复发有关的机制尚未明确。我们测试了这样的假设：在已经形成背外侧纹状体（DLS）依赖的线索控制的可卡因寻求习惯的个体中，在戒断期间失去执行药物寻求反应的机会会导致采取行动的冲动，从而加剧介导的复发严重程度通过消极的紧迫感。

 方法

87 只雄性斯普拉格道利大鼠被训练在药物配对线索的条件强化特性的影响下寻找可卡因。我们调查了复发的倾向是否取决于戒断的厌恶状态，或者是否取决于戒断一段时间后失去进行根深蒂固的寻求药物反应的机会。使用细胞活性标记物C -fos的原位杂交，研究了基线和复发时对可卡因寻求的控制的纹状体位点，并评估了寻求工具药物对背内侧纹状体中多巴胺受体阻断的敏感性——目标导向和 DLS -依赖的习惯系统。

 结果

戒断前 DLS 依赖性线索控制的可卡因寻求习惯的发展导致复吸时寻求药物的显着增加，这不是由可卡因戒断状态驱动的，也不再依赖于 DLS 习惯系统。相反，它反映了由于禁欲期间习惯的表现受到阻碍而导致的负面紧迫性的出现，并以目标导向系统的短暂参与为基础。

 结论

这些结果表明根深蒂固的线索控制的寻求药物的习惯会增加复发的压力。