Cocaine abstinence induces emotional impairment and brain region-specific upregulation of the oxytocin receptor binding
Cocaine abstinence induces emotional impairment and brain region-specific upregulation of the oxytocin receptor binding
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DOI：
10.1111/ejn.13348
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发表时间：
2016-10-01
影响因子：
3.4
通讯作者：
Bailey, Alexis
中科院分区：
文献类型：
--
作者：
Georgiou, Polymnia;Zanos, Panos;Bailey, Alexis
治疗可卡因成瘾的关键问题是维持戒毒状态，因为戒断期间的负面情绪症状往往会引发复发。目前尚不清楚禁欲期间情绪失调的机制。有证据表明神经肽催产素在调节药物成瘾过程中发挥作用。然而，其在长期戒除可卡因使用过程中的作用仍不清楚。在这项研究中，我们的目的是对长期可卡因戒断的小鼠模型进行行为特征分析，并评估长期可卡因给药和长期可卡因戒断对中枢催产素系统和下丘脑-垂体-肾上腺轴的影响。 14 天递增剂量可卡因给药（3x15-30mg/kg/天）和 14 天停药可增加血浆皮质酮水平以及梨状皮层、侧隔膜和杏仁核中催产素受体 (OTR) 的结合。在内侧隔膜中观察到可卡因戒断诱导的 OTR 结合特异性增加。这些生化改变伴随着戒断期间记忆障碍、情境精神运动敏化以及快感缺乏和焦虑表型的出现而发生。我们的研究在可卡因戒断的新型翻译相关模型中建立了可卡因戒断与情绪障碍之间的明确关系，并首次证明了催产素系统的大脑区域特异性神经适应，这可能导致戒断引起的负面情绪状态。
The key problem in treating cocaine addiction is the maintenance of a drug-free state as negative emotional symptoms during abstinence often trigger relapse. The mechanisms underpinning the emotional dysregulation during abstinence are currently not well-understood. There is evidence suggesting a role of the neuropeptide oxytocin in the modulation of drug addiction processes. However, its involvement during long-term abstinence from cocaine use remains unclear. In this study, we aimed to behaviourally characterize a mouse model of long-term cocaine withdrawal and assess the effect of chronic cocaine administration and long-term cocaine abstinence on the central oxytocinergic system and the hypothalamic-pituitary-adrenal axis. Fourteen-day escalating-dose cocaine administration (3x15-30mg/kg/day) and 14-day withdrawal increased plasma corticosterone levels and oxytocin receptor (OTR) binding in piriform cortex, lateral septum and amygdala. A specific cocaine withdrawal-induced increase in OTR binding was observed in the medial septum. These biochemical alterations occurred concomitantly with the emergence of memory impairment, contextual psychomotor sensitization and an anhedonic and anxiogenic phenotype during withdrawal. Our study established a clear relationship between cocaine abstinence and emotional impairment in a novel translationally relevant model of cocaine withdrawal and demonstrated for the first time brain region-specific neuroadaptations of the oxytocin system, which may contribute to abstinence-induced negative emotional state.