Inactivation of the infralimbic cortex decreases discriminative stimulus-controlled relapse to cocaine seeking in rats
Inactivation of the infralimbic cortex decreases discriminative stimulus-controlled relapse to cocaine seeking in rats
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DOI：
10.1038/s41386-021-01067-6
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发表时间：
2021-06-23
影响因子：
7.6
通讯作者：
Hope, Bruce T.
中科院分区：
文献类型：
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作者：
Madangopal, Rajtarun;Ramsey, Leslie A.;Hope, Bruce T.
对提示诱发的复发的持续易感性是成瘾的一个主要特征。辨别刺激 (DS) 是一种与药物相关的线索，可发出药物可用性 (DS+) 或不可用 (DS-) 信号，并在复发前控制药物寻求。我们之前在大鼠中建立了一种基于试验的程序，在可卡因自我给药期间将 DS 与背景、条件刺激和其他药物相关线索分离，并证明 DS 控制的可卡因寻求长达 300 的戒断天数。基于试验的药物寻求 DS 控制的行为和神经机制很少被研究。在这里，我们表明，在基于试验的程序中进行辨别训练后，DS+和DS-在戒断期间独立控制可卡因寻求的表达和抑制。通过在内侧前额叶皮质中显微注射 GABA(A) + GABA(B) 受体激动剂（蝇蕈醇 + 巴氯芬），我们报告说，内侧前额叶皮质的下边缘（而非前边缘）亚区域对于长期戒断后寻求可卡因的持续 DS 控制的复发至关重要，但不是 DS 引导的歧视 可卡因寻求或 DS 控制的可卡因自我给药。最后，利用内侧前额叶皮层锥体神经元的离体全细胞记录，我们证明，在边缘下皮层微量注射蝇蕈醇+巴氯芬后，DS控制的可卡因寻找的破坏可能是通过突触前作用机制抑制该区域突触传递的结果。
Persistent susceptibility to cue-induced relapse is a cardinal feature of addiction. Discriminative stimuli (DSs) are one type of drug-associated cue that signal drug availability (DS+) or unavailability (DS-) and control drug seeking prior to relapse. We previously established a trial-based procedure in rats to isolate DSs from context, conditioned stimuli, and other drug-associated cues during cocaine self-administration and demonstrated DS-controlled cocaine seeking up to 300 abstinence days. The behavioral and neural mechanisms underlying trial-based DS-control of drug seeking have rarely been investigated. Here we show that following discrimination training in our trial-based procedure, the DS+ and DS- independently control the expression and suppression of cocaine seeking during abstinence. Using microinjections of GABA(A) + GABA(B) receptor agonists (muscimol + baclofen) in medial prefrontal cortex, we report that infralimbic, but not prelimbic, subregion of medial prefrontal cortex is critical to persistent DS-controlled relapse to cocaine seeking after prolonged abstinence, but not DS-guided discriminated cocaine seeking or DS-controlled cocaine self-admininstration. Finally, using ex vivo whole-cell recordings from pyramidal neurons in the medial prefrontal cortex, we demonstrate that the disruption of DS-controlled cocaine seeking following infralimbic cortex microinjections of muscimol+baclofen is likely a result of suppression of synaptic transmission in the region via a presynaptic mechanism of action.