摘要
目的建立条件性位置偏爱模型,检测吗啡精神依赖大鼠不同脑区中氨基酸类神经递质含量的变化。方法用4mg·kg-1盐酸吗啡对雄性SD大鼠进行条件性位置偏爱(CPP)训练。CPP形成后将大鼠断头处死,立即取脑,分离杏仁核、额叶皮层、海马、下丘脑、伏隔核、纹状体、丘脑、小脑等8个核团,在高氯酸溶液中做组织匀浆,同时沉淀蛋白,离心后取上清液备测。采用柱前衍生-电化学检测-高效液相色谱法测定谷氨酸(GLU)和γ-氨基丁酸(GABA)含量。结果吗啡使大鼠形成CPP时,额叶皮层、下丘脑和伏隔核的GLU和GABA含量均有明显下降(P<0.05),其中以伏隔核变化最明显(P<0.01);而且,伏隔核中的GLU/GABA值显著升高(P<0.05)。结论大鼠对吗啡的精神依赖形成时,中枢GLU和GABA的含量变化集中于额叶皮层、下丘脑和伏隔核等与奖赏作用关系密切的脑区,证明了GLU和GABA系统参与了精神依赖形成时药物在脑内的奖赏作用。伏隔核中的GABA含量显著下降,GLU/GABA值显著升高,表明吗啡精神依赖时伏隔核处于去抑制状态。
Aim To investigate the changes of amino acids levels in brain regions of morphine psychical dependent rats. Methods Conditioned place preference (CPP) was established in Sprague Dawley rats with morphine hydrochloride (4mg·kg^-1) training. Brain tissues were dissected out and homogenized. Proteins were precipitated and pelleted by centnfugation. The supernatants were diluted to a suitable concentration before derivatization. Brain regions selected were amygdala, frontal cortex, hippocampus, hypothalamus, nucleus accumbens, striatum, thalamus and cerebellum. The contents of glutamate (GLU) and gamma-aminobutyric acid (GABA) were quantitated by HPLC-ECD with precolumn derivatization. Results In brains of morphine trained rats, the contents of both GLU and GABA significantly decreased in frontal cortex, hypothalamus and nucleus accumbens ( P 〈 0.05), while the ratio of GLU/GABA significantly increased in nucleus accumbens ( P 〈 0.05). Conclusion GLU and GABA levels were changed in rat brain after training. The results suggest that GLU and/or GABA system may participate in the rewarding effect of morphine during establishment psychical dependence. The nucleus accumbens were in disinhibited condition in morphine CPP rats for the content of GABA decreased significantly and the ratio of GLU/GABA increased significantly.
出处
《解放军药学学报》
CAS
2005年第4期248-251,共4页
Pharmaceutical Journal of Chinese People's Liberation Army
关键词
吗啡
精神依赖
条件性位置偏爱
谷氨酸
Γ-氨基丁酸
Morphine
Psychical dependence
Conditioned place preference
Glutamate
Gamma-aminobutyric acid