Persistent strengthening of the prefrontal cortex – nucleus accumbens pathway during incubation of cocaine-seeking behavior
Persistent strengthening of the prefrontal cortex – nucleus accumbens pathway during incubation of cocaine-seeking behavior
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DOI：
10.1016/j.nlm.2016.10.003
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发表时间：
2017-02
影响因子：
2.7
通讯作者：
Catarina Luís;N. Cannella;R. Spanagel;G. Köhr
中科院分区：
文献类型：
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作者：
Catarina Luís;N. Cannella;R. Spanagel;G. Köhr
长期戒断后的高复发率通常是由于暴露于诱发药物渴望的药物相关线索而引发的。药物渴望的潜伏期是一种现象，包括戒断期间线索诱导的药物渴望的时间依赖性增加。伏隔核（NAc）的可塑性机制是药物寻找反应的基础，并涉及兴奋性突触传递效力的变化。特别是，前额叶皮层（PFC）的谷氨酸能输入到NAc核心，在非偶然或偶然暴露于可卡因或长期戒断后的可卡因诱发可塑性方面已经得到了很好的表征。尽管如此，与drug-naïve条件相比，戒断过程中的突触强度尚不清楚，因为电生理特征主要是在脑切片中进行的，或者集中在体内可卡因诱发可塑性的不同时间点。在这里，我们使用了一个孵育模式，其中大鼠延长了可卡因自我给药的时间，并在戒断第1天和第30天进行了提示诱导恢复。清醒大鼠体内电位的纵向记录显示，与未接触可卡因的情况相比，慢性偶然暴露于可卡因的大鼠边缘前区PFC到NAc核心通路增强。这种增强与成对脉冲比（PPR）的降低有关，这表明突触前谷氨酸释放的增强，在整个戒断过程中持续存在。此外，慢性可卡因暴露后的场电位增加和PPR降低都与训练期间接受可卡因输注的次数有关。目前的研究结果和之前的研究结果表明，PFC-NAc核心通路的戒断依赖性突触后增强表明，在寻求药物的大鼠中，在自我给药期间开始了额外的突触前增强，并在整个戒断期间保持。这些可卡因驱动的神经适应可能为不适应的线索处理提供了神经基质，最终会引发渴望和复发。
High rates of relapse after prolonged abstinence are often triggered by exposure to drug-associated cues that induce drug craving. Incubation of drug craving is a phenomenon that consists of time-dependent increases in cue-induced drug craving during withdrawal. Plasticity mechanisms in the nucleus accumbens (NAc) underlie drug-seeking responses and involve changes in excitatory synaptic transmission’s efficacy. In particular, the prefrontal cortex (PFC) glutamatergic input to the NAc core has been well characterized regarding cocaine-evoked plasticity following non-contingent versus contingent exposure to cocaine or alternatively after protracted abstinence. Still, the synaptic strength during the course of withdrawal compared to drug-naïve condition is unknown, since electrophysiological characterizations are mainly performed in brain slices or focus on distinct time points during cocaine-evoked plasticityin vivo. Here we used an incubation paradigm, in which rats had extended accessed to cocaine self-administration, and underwent cue-induced reinstatement at withdrawal day 1 and 30. Longitudinalin vivofield potential recordings in awake rats showed that chronic contingent exposure to cocaine strengthened the prelimbic PFC to NAc core pathway when compared to pre-cocaine condition. This strengthening was associated with decreased paired-pulse ratios (PPR), indicative of presynaptic enhancement of glutamate release, which persisted throughout withdrawal. Moreover, both field potential increase and PPR reduction after chronic cocaine exposure correlated with the number of cocaine infusions received during training. The present results together with previous findings of withdrawal-dependent postsynaptic enhancement of the PFC-NAc core pathway, suggest an additional presynaptic strengthening that is initiated during self-administration and maintained throughout abstinence in drug-seeking rats. These cocaine-driven neuroadaptations may provide a neural substrate for maladaptive processing of cues that can ultimately trigger craving and relapse.