Brief social defeat stress:: Long lasting effects on cocaine taking during a binge and Zif268 mRNA expression in the amygdala and prefrontal cortex
Brief social defeat stress:: Long lasting effects on cocaine taking during a binge and Zif268 mRNA expression in the amygdala and prefrontal cortex
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DOI：
10.1038/sj.npp.1300587
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发表时间：
2005-02-01
影响因子：
7.6
通讯作者：
Miczek, KA
中科院分区：
文献类型：
--
作者：
Covington, HE;Kikusui, T;Miczek, KA
社会压力会引起行为和神经敏感，这一过程似乎会加速向强迫性药物滥用的转变。大鼠暴露于短暂的社交失败压力对可卡因强化行为和中皮质边缘多巴胺系统区域的功能激活水平具有显着影响。当前研究的目的是检查短暂的社交失败压力对可卡因暴饮暴食（连续 24 小时内）的持久影响，以及 zif268 早期基因表达所揭示的神经适应的出现。成年雄性 Long-Evans 大鼠经历四次 25 分钟的社交失败（每 72 小时一次）。 2 个月后，在确认对刺激物挑战的行为交叉敏感性后，研究了可卡因暴食或 zif268 mRNA 基因表达。对社交失败的敏感性增加了 24 小时暴食期间可卡因的摄入量，有效地消除了典型的昼夜节律摄入模式。此外，在接受社交失败致敏方案60天后，中央和内侧杏仁核的功能激活水平（通过zif268 mRNA表达测量）增加，而内侧前额叶皮层的激活水平降低。注射安非他明（1.0 mg/kg）可减弱中央和内侧杏仁核中持续应激诱导的 zif268 水平。社交失败压力后两个月，杏仁核和皮质内 zif268 的不同变化表明调节精神运动兴奋剂行为的网络中不同细胞群的脆弱性。
Social stress can engender behavioral and neural sensitization and this process appears to enhance the transition to compulsive drug abuse. Exposures to brief social defeat stress in rats have significant consequences on cocaine-reinforced behavior and on the level of functional activation within regions of the mesocorticolimbic dopamine system. The objectives of the current study were to examine the enduring consequences of brief episodes of social defeat stress on cocaine bingeing ( during 24 h of continuous access) and on the emergence of neural adaptations as revealed by zif268 immediate early gene expression. Adult, male Long - Evans rats were subjected to four 25 min episodes of social defeat ( once every 72 h). After 2 months, cocaine binges or zif268 mRNA gene expression were studied after confirming behavioral cross-sensitization to stimulant challenge. Sensitization to social defeat increased cocaine intake during a 24 h binge, effectively abolishing the typical circadian pattern of intake. Furthermore, 60 days after exposure to the sensitizing regimen of social defeat, levels of functional activation, measured by zif268 mRNA expression, in the central and medial amygdala were increased, while levels of activation in the medial prefrontal cortex were decreased. Persistent stress-induced levels of zif268 in the central and medial amygdala were attenuated by an injection of amphetamine (1.0 mg/kg). Divergent changes in zif268 within the amygdala and cortex 2 months after social defeat stress indicate the vulnerability of distinct cellular populations in networks that modulate the behavioral actions of psychomotor stimulants.