药物成瘾记忆再巩固过程中脑内Zif268的激活

Activation of brain Zif 268 in process of drug addictive memory reconsolidation

目的探讨药物成瘾记忆再巩固过程中的具体分子机制，阐明其中的关键分子。方法成年雄性SD大鼠30只按照随机数字表法分为生理盐水组（n=8）和可卡因组（n=22）；有效建立可卡因条件位置偏爱模型后，将可卡因组已明显成瘾的大鼠（n=151按照随机数字表法分成对照组（n=7）和成瘾记忆再巩固刺激组（n=8）。免疫组化染色检测3组大鼠脑内Zif268在可卡因诱导的成瘾记忆再巩固刺激后的表达情况。结果可卡因诱导的成瘾记忆再巩固刺激后大脑内侧前额叶皮质（mPFC）、伏隔核（NAcl、海马、杏仁核及乳头体上核（SUM）部位Zif268被激活，这些脑区表达Zif268的神经细胞数量比对照组显著升高，差异有统计学意SL（tmerC=12．640，tn=18．460，tNAc-corre=18．470，tNAc-shell=19．860，tCA1=17．860，tCA2=15．360，tcm=6．671，t杏仁核=15．570，tsar=20．380，P=-0．000）。结论大脑内侧前额叶皮质、伏隔核、海马、杏仁核及乳头体上核部位Zif268在药物成瘾记忆再巩固刺激后被显著激活，成瘾相关环路上的Zif268参与介导了药物成瘾记忆再巩固的过程。

Objective Memory reconsolidation plays an important role in the process of drug addiction. Effective intervention on memory reconsolidation process is expected to be important treatment for drug addiction. This experiment aims to explore specific molecular mechanism in memory reconsolidation of drug addiction and to clarify the key molecules. Methods Thirty adult male Sprague-Dawley rats were chosen and divided into two groups according to random number table method： saline group （n=8） and cocaine group （n=22）. After cocaine conditioned place preference was built, addicted rats in the cocaine group （n=15） were divided into two subgroups： control group （n=7） and reconsolidation stimulus group （n=8） in the same method. Immunohistochemical method was empoyed to study the changes of brain Zif 268 expression in the process of drug addictive memory reconsolidation induced by cocaine. Results After being cocaine addictive memory reconsolidated, Zif 268 was widely activated in medial prefrontal cortex （mPFC）, accumbens nucleus （NAc）, hippocampus, amygdala, supramammillary nucleus （SUM）; and the number ofZif268 immunohistochemical positive neurons in them increased significantly as compared with that in the control group （tmPFC=12.64, tIL=18.46, tNAc-core= 18.470, tNAc-shell=19.860, tCA1=17.860, tCA2=15.360, tCA3=6.671, tamygdala=15.570, tSuM=20.380, P=-0.000）. Conclusion Zif268 in mPFC, NAc, hippocampus, amygdala, SuM plays an important role in the process of drug addictive memory reconsolidation.