Wang Jun-Jun, Yao Wen-Qing, Chen Yue-Jun, Ma Lan, Tao Ye-Zheng
The State Key Laboratory of Medical Neurobiology and Pharmacology Research Center, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China.
Sheng Li Xue Bao. 2014 Oct 25;66(5):545-58.
The intense associative memories that develop between cocaine-paired contexts and rewarding stimuli make addiction hard to cure by contributing to cocaine seeking and relapse. So it's of great importance to examine the neurobiological basis of addiction memory. Cocaine conditioned place preference (CPP) used in this study is a form of Pavlovian conditioning which can establish associations between drug and contextual factors. c-Fos and Zif268 are commonly used immediate early gene (IEG) makers to identify neurons that are activated after a stimulus or behavioral conditioning. This study was designed to reveal neuronal c-Fos, Zif268 expression pattern in 10 brain regions following cocaine context-associated reward memory retrieval in mice, combining animal behavioral study and immunofluorescence method. C57BL/6 mice were randomly divided into 3 groups: Saline retrieval, Cocaine retrieval, and No retrieval of cocaine groups. Cocaine retrieval and No retrieval of cocaine underwent CPP training (one side paired with cocaine, and the other side with saline) except that No retrieval of cocaine group didn't undergo CPP test. Saline retrieval group received saline injections (i.p) on both sides. The results showed that: Neuronal c-Fos, Zif268 protein expression levels in nucleus accumbens (NAc) core both were elevated in Cocaine retrieval group compared with those in Saline retrieval (Control) group during cocaine context-associated reward memory retrieval. Zif268 protein expression level in basolateral amygdala (BLA) was also elevated in Cocaine retrieval group compared with that in control mice. Elevation was not seen in other regions such as hippocampus, prefrontal cortex (PFC). Thus, NAc core and BLA were activated during cocaine context-associated reward memory retrieval. The results suggest that neurons that are activated in NAc core and BLA are crucial basis of cocaine context-associated reward memory.
在可卡因配对环境与奖赏刺激之间形成的强烈关联记忆，通过促使对可卡因的寻觅和复吸，使得成瘾难以治愈。因此，研究成瘾记忆的神经生物学基础至关重要。本研究中使用的可卡因条件性位置偏爱（CPP）是一种经典条件反射形式，它能够在药物与环境因素之间建立联系。c-Fos和Zif268是常用的即时早期基因（IEG）标记物，用于识别在刺激或行为条件反射后被激活的神经元。本研究旨在结合动物行为学研究和免疫荧光方法，揭示小鼠在与可卡因环境相关的奖赏记忆检索后，10个脑区中神经元c-Fos、Zif268的表达模式。C57BL/6小鼠被随机分为3组：生理盐水检索组、可卡因检索组和未检索可卡因组。可卡因检索组和未检索可卡因组接受CPP训练（一侧与可卡因配对，另一侧与生理盐水配对），只是未检索可卡因组不进行CPP测试。生理盐水检索组两侧均接受腹腔注射生理盐水。结果显示：在与可卡因环境相关的奖赏记忆检索过程中，与生理盐水检索（对照）组相比，可卡因检索组伏隔核（NAc）核心区的神经元c-Fos、Zif268蛋白表达水平均升高。与对照小鼠相比，可卡因检索组基底外侧杏仁核（BLA）的Zif268蛋白表达水平也升高。在海马、前额叶皮质（PFC）等其他区域未观察到表达升高。因此，在与可卡因环境相关的奖赏记忆检索过程中，NAc核心区和BLA被激活。结果表明，在NAc核心区和BLA中被激活的神经元是与可卡因环境相关的奖赏记忆的关键基础。
