Changes in expression of c-Fos protein following cocaine-cue extinction learning.
Changes in expression of c-Fos protein following cocaine-cue extinction learning.
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DOI：
10.1016/j.bbr.2012.06.010
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发表时间：
2012-09-01
影响因子：
2.7
通讯作者：
Kantak, K. M.
中科院分区：
文献类型：
--
作者：
Dhonnchadha, B. A. Nic;Lovascio, B. F.;Shrestha, N.;Lin, A.;Leite-Morris, K. A.;Man, H. Y.;Kaplan, G. B.;Kantak, K. M.
消除对滥用药物相关线索的异常强化的习得反应仍然是缓解成瘾的关键策略。为了协助开发药物疗法以增强暴露疗法以预防复发，需要对药物提示消退学习的神经生物学基础进行研究。我们使用 c-Fos 和 GluR2 蛋白表达的区域分析来描绘可能与可卡因提示消退学习相关的神经活动和可塑性。训练大鼠自我注射可卡因并搭配光提示，随后进行一次 2 小时的灭绝疗程，其中可卡因被抑制，但呈现反应相关线索（可卡因提示灭绝）。对照组由与动物结合的大鼠组成，这些大鼠自我施用可卡因并非偶然地接受盐水，然后进行灭绝过程，或者训练大鼠自我施用可卡因，然后进行非灭绝过程，在该过程中拉杆被收回，可卡因和提示被扣留。在检查的 11 个大脑部位中，相对于两种对照条件，灭绝训练增加了可卡因提示灭绝大鼠的基底外侧杏仁核和前边缘前额叶皮质中的 c-Fos 表达。在背下托和边缘下前额皮质中，相对于非消退对照条件，消退训练增加了可卡因提示和盐水提示熄灭大鼠的 c-Fos 表达。在消退或对照训练后检查的任何部位，GluR2 蛋白表达均未改变。研究结果表明，基底外侧杏仁核和前边缘前额叶皮层神经元在获得可卡因提示消退学习过程中被激活，这一过程与 GluR2 丰度的变化无关。其他站点涉及处理消退训练早期出现的线索的重要性。
Extinguishing abnormally strengthened learned responses to cues associated with drugs of abuse remains a key tactic for alleviating addiction. To assist in developing pharmacotherapies to augment exposure therapy for relapse prevention, investigation into neurobiological underpinnings of drug-cue extinction learning is needed. We used regional analyses of c-Fos and GluR2 protein expression to delineate neural activity and plasticity that may be associated with cocaine-cue extinction learning. Rats were trained to self-administer cocaine paired with a light cue, and later underwent a single 2hr extinction session for which cocaine was withheld but response-contingent cues were presented (cocaine-cue extinction). Control groups consisted of rats yoked to animals self-administering cocaine and receiving saline non-contingently followed by an extinction session, or rats trained to self-administer cocaine followed by a no-extinction session for which levers were retracted, and cocaine and cues were withheld. Among 11 brain sites examined, extinction training increased c-Fos expression in basolateral amygdala and prelimbic prefrontal cortex of cocaine-cue extinguished rats relative to both control conditions. In dorsal subiculum and infralimbic prefrontal cortex, extinction training increased c-Fos expression in both cocaine-cue and saline-cue extinguished rats relative to the no-extinction control condition. GluR2 protein expression was not altered in any site examined after extinction or control training. Findings suggest that basolateral amygdala and prelimbic prefrontal cortex neurons are activated during acquisition of cocaine-cue extinction learning, a process that is independent of changes in GluR2 abundance. Other sites are implicated in processing the significance of cues that are present early in extinction training.
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影响因子：
2
作者：
Laurent, Vincent;Westbrook, R. Frederick
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.98.4.1976
发表时间：
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影响因子：
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Dhonnchadha, Brid A. Nic;Szalay, Jonathan J.;Achat-Mendes, Cindy;Platt, Donna M.;Otto, Michael W.;Spealman, Roger D.;Kantak, Kathleen M.
通讯作者：
Kantak, Kathleen M.
影响因子：
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