阿片类药物对海马神经递质释放调控的分子机制  

MOLECULAR MECHANISMS FOR REGULATION OF NEUROTRANSMITTER RELEASE BY OPIATES IN HIPPOCAMPUS

作　　者：李玉婷[1] 鲍国斌[1] 余甬新[1] 范春妹[1] 马兰[2] 裴钢[2] 

机构地区：[1]中国科学院上海生化细胞所,上海200031 [2]复旦大学药理研究中心,上海200032

出　　处：《中国药物依赖性杂志》2006年第3期213-216,共4页Chinese Journal of Drug Dependence

基　　金：国家重点基础研究发展计划(973计划)"精神活性物质依赖的生物学基础及防治"(2003CB515400)资助项目

摘　　要：阿片类药物的滥用,可导致脑内神经元的长时程适应,从而产生严重的身体依赖和心理依赖。越来越多的证据表明,阿片类药物所引起的这种适应性变化会影响突触前神经递质的释放,并改变包括谷氨酸能神经系统在内的神经元的功能。我们的研究表明,在海马这个富含谷氨酸能神经元的脑区,阿片类药物如吗啡的长期使用,会引起胞外谷氨酸水平的持续改变。进一步的研究表明,该脑区的SNARE蛋白复合物发生了适应性的改变。SNARE蛋白家族是重要的调节神经可塑性的调节分子,在神经递质释放过程中起重要作用。在吗啡长期处理过程中,SNAP-25的色氨酸187位点的磷酸化明显下降,SNARE复合物的形成受到抑制。我们的结果揭示了阿片类药物可通过调控突触前直接参与递质释放的分子来影响递质本身释放这一分子机制。Opiate abuse, associated with long- lasting neural adaptive changes in presynaptic release in the brain can induce severe physiological and psychological dependence. Increasing evidence suggests that opiates can alter the functions of glutamatergic system. Our researches find that in rodent hippocampus, a nucleus rich in glutamatergic neurons, chronic application of opiate such as morphine can modulate extracelluar levels of glutamate. And our further findings on neuronal SNARE protein, an important regulatory molecules underlying neural plasticity in view of their major role in the process of neurotransmitter release, show that during chronic morphine treatment, inhibited and SNARE complex formation is down - phosphorylation of SNAP -25 at Ser187 is significantly regulated. Thus, our findings present us a potential molecular mechanism which may regulate the alteration of neurotransmitter level during opiate abuse.

关 键 词：阿片 海马 神经可塑性 谷氨酸 

分 类 号：R338[医药卫生—人体生理学] R971.1[医药卫生—基础医学]