Differential expression of Arc in the mesocorticolimbic system is involved in drug and natural rewarding behavior in rats
Differential expression of Arc in the mesocorticolimbic system is involved in drug and natural rewarding behavior in rats
复制标题
DOI：
10.1038/aps.2013.28
复制
发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Mu Li;Wenjing Liu;Bin Lu;Yu-hua Wang;Jing-Gen Liu
中科院分区：
文献类型：
--
作者：
Mu Li;Wenjing Liu;Bin Lu;Yu-hua Wang;Jing-Gen Liu
目的：研究海洛因和牛奶在激活在奖赏强化学习中起关键作用的皮质纹状体系统方面的不同作用。方法：雄性SD大鼠每天训练15d，在经典的跑道药物自我给药模型中自我给药海洛因或牛奶片。用免疫组织化学方法检测慢性给药后大鼠内侧前额叶皮质(MPFC)、伏隔核(NAC)、背内侧纹状体(DMS)和腹外侧纹状体(VLS)Arc蛋白的表达。结果：海洛因跑道训练使d1、d1、mPFC、NAC和DMS的Arc表达增强，d1、d7和d7的VLS Arc蛋白表达增强，而牛奶跑道训练仅在d7和/或d15使mPFC、NAC和DMS的Arc表达增加，但在d1无明显变化。MK801和SCH23390均可抑制海洛因寻找行为和Arc蛋白的表达。结论：VLS可能在海洛因寻找行为中起重要作用。依赖NMDA和D1R的Arc表达在药物寻找行为中起重要作用。
Aim:To investigate the different effects of heroin and milk in activating the corticostriatal system that plays a critical role in reward reinforcement learning.Methods:Male SD rats were trained daily for 15 d to self-administer heroin or milk tablets in a classic runway drug self-administration model. Immunohistochemical assay was used to quantify Arc protein expression in the medial prefrontal cortex (mPFC), the nucleus accumbens (NAc), the dorsomedial striatum (DMS) and the ventrolateral striatum (VLS) in response to chronic self-administration of heroin or milk tablets. NMDA receptor antagonist MK801 (0.1 mg/kg) or dopamine D1 receptor antagonist SCH23390 (0.03 mg/kg) were intravenously injected at the same time as heroin was infused intravenously.Results:Runway training with heroin resulted in robust enhancement of Arc expression in the mPFC, the NAc and the DMS on d 1, 7, and 15, and in the VLS on d 1 and d 7. However, runway training with milk led to increased Arc expression in the mPFC, the NAc and the DMS only on d 7 and/or d 15 but not on d 1. Moreover, runway training with milk failed to induce increased Arc protein in the VLS. Both heroin-seeking behavior and Arc protein expression were blocked by MK801 or SCH23390 administration.Conclusion:The VLS is likely to be critically involved in drug-seeking behavior. The NMDA-and D1 receptor-dependent Arc expression is important in drug-seeking behavior.