内侧前额叶皮层神经元可塑性改变在吗啡奖赏记忆形成中的作用 |
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引用本文: | 吕秀芳,;胡宝英,;巩秀,;王晓冬. 内侧前额叶皮层神经元可塑性改变在吗啡奖赏记忆形成中的作用[J]. 中国行为医学科学, 2014, 0(12): 1061-1064 |
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作者姓名: | 吕秀芳, 胡宝英, 巩秀, 王晓冬 |
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作者单位: | [1]南通大学医学院基础医学研究室,南通226001; [2]南通大学医学院组织胚胎学教研室,南通226001 |
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基金项目: | 国家自然科学基金资助项目(81271721);南通大学自然科学类科研基金前期预研项目(12ZY013) |
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摘 要: | 目的 观察吗啡诱导的大鼠内侧前额叶皮质(mPFC)神经元可塑性改变对吗啡奖赏记忆形成的影响.方法 40只SD大鼠分为生理盐水对照组和吗啡组,分别腹腔注射生理盐水(2 ml/kg)和盐酸吗啡(10 mg/kg),注射后0、2、4、8h断头取脑,Western Blot分析mPFC区Arc/Arg 3.1蛋白变化;另取大鼠60只,分别腹腔注射0、5、10或20 mg/kg吗啡,Western Blot(n=5)分析mPFC区Arc/Arg 3.1蛋白变化;免疫组化法(n=5)检测mPFC区Arc/Arg 3.1阳性细胞数量变化;Golgi-cox改良法(n=5)检测mPFC区神经元棘突数量变化;再取大鼠40只,经8天生理盐水、吗啡交替训练建立条件性位置偏爱(CPP)模型,吗啡模型组大鼠在每次吗啡注射前15 min给予mPFC区注射Arc/Arg 3.1基因的反义寡核苷酸(AS,n=10)及其对照(CS,n=10),观察其对吗啡CPP评分的影响.结果 与生理盐水对照组相比,10 mg/kg吗啡注射后2 h mPFC内Arc/Arg 3.1蛋白水平、Arc/Arg 3.1阳性细胞数、棘突数量[(1.01±0.04) vs (1.58±0.18),P<0.01;(42.80±7.63) vs (74.47±8.02),P<0.01;(17.27±5.64) vs (39.47±7.56),P<0.01]均显著增加;与对照组相比,5、10或20 mg/kg吗啡注射后2h均可诱导mPFC的Arc/Arg 3.1蛋白水平显著增加,无剂量依赖效应;对于吗啡CPP模型组大鼠,与mPFC区注射CS相比(0.74±0.02),AS显著降低吗啡CPP的评分(0.51±0.01),差异具有统计学意义(P<0.01).结论 单次吗啡注射可以诱导大鼠mPFC区Arc/Arg 3.1蛋白表达增加并伴有神经元可塑性的增强,增加的Arc/Arg 3.1蛋白介导了吗啡奖赏记忆的形成.
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关 键 词: | 吗啡 内侧前额叶皮质 突触可塑性 成瘾记忆 条件性位置偏爱 |
Effect of mPFC neuron synaptic plasticity changes in the formation of morphine related reward memory |
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Affiliation: | Lyu Xiufang, Hu Baoying, Gong Xiu, Wang Xiaodong (Basic Medical Research Centre in Medical College of Nantong University, Nantong 226001, China) |
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Abstract: | Objective To observe the effect of mPFC neuron synaptic plasticity changes in the formation of morphine related reward memory.Methods 40 SD rats were administered morphine (10 mg/kg,ip) or saline (2 ml/kg,ip)and sacrificed 0,2,4 and 8 h after the treatment.The temporal profile of activity-regulated cytoskeleton-associated protein (Arc/Arg 3.1) expression in medial prefrontal cortex (mPFC) was analyzed.Another 40 rats receiving a single injection of morphine at different doses (0,5,10 or 20 mg/kg),and rats were sacrificed by decapitation 2 h later.In mPFC,changes of Arc/Arg 3.1 protein was analyzed by Western Blot,Arc/Arg 3.1 positive cells was detected by immunohistochemistry (IHC),and number of spines were analyzed by Golgi-cox method.In the second experiment,CPP model was established by 5 mg/kg morphine for 8 days.Arc/Arg 3.1 antisense oligodeoxynucleotide (AS) or the control (CS) was microinjected into mPFC 15 minutes before each morphine injection,then CPP score was evaluated.Results Compared with saline groups,Arc/Arg 3.1 protein,Arc/Arg 3.1 positive cells,number of spines ((1.01±0.04) vs (1.58±0.18),P〈0.01 ; (42.80±7.63) vs (74.47±8.02),P〈0.01 ;(17.27±5.64) vs (39.47±7.56),P〈0.01) were significantly increased 2 hours after morphine administration.All three doses of morphine (5,10 and 20 mg/kg) increased Arc/Arg 3.1 protein expression in the mPFC,and there were no dose-dependent effects.In CPP experiments,compared with microinjection of Arc/Arg 3.1 CS (0.74±0.02),Arc/Arg 3.1 AS microinjection significantly decreased the CPP score (0.51±0.01) in morphine group (P〈0.01).Conclusion It is enough to increase Arc/Arg 3.1 protein content and synaptic plasticity in mPFC by 10 mg/kg,and the changes implied in formation of morphine relative reward memory. |
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Keywords: | Morphine Medial prefrontal cortex (mPFC) Synaptic plasticity Addiction memory Conditioned place preference (CPP) |
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