【摘要】 中脑－边缘ＤＡ神经系统在阿片奖赏效应中起着关键性作用。长期应用阿片类药物可引起该系统靶神经元独特的适应性改变，主要包括：（１）中脑腹侧被盖区（ＶＴＡ）的ＴＨ被诱导增加、ＧｌｕＲ１受体上调、神经纤维丝蛋白的减少以及ＤＡ神经元的形态萎缩等；（２）伏核（ＮＡｃ）ＤＡＤ１受体超敏、Ｇｉ／ｏａ亚单位的减少、ｃＡＭＰ－ＰＫＡ系统活性上调以及ｃＡＭＰ反应元蛋白（ＣＲＥＢ）和ｃ－ｆｏｓ、ｃ－ｊｕｎ基因表达的改变等。阿片类物质通过和受体的不同作用，直接或间接地改变ＶＴＡ－ＮＡｃＤＡ神经系统的功能活动，从而强化脑内奖赏系统或产生负性效应。神经营养因子和转基因技术的应用，进一步揭示中脑－边缘ＤＡ系统的适应性变化是阿片成瘾精神依赖形成的重要基础。更多还原

【Abstract】 The mesolimbic dopamine system, which plays an important role in the reinforcingeffects of opiates reward, has been shown specific cellular adaptations in responses to chronic opiateadministration. These adaptations have been included: (1) the higher levels of tyrosine hydrox-ylase (TH), upregulation of GluR1, lower levels of neurofilament proteins and a reduction of thesize of dopamine neurons in the ventral tegmental area (VTA); (2) the functional D1-receptor su-persensitivity, decreased levels of Gi/o a subunits, increased levels of cAMP-PKA system and theupregulation of the nuclear transcription factors CREB, c-fos and c-jun expression in the nucleusaccumbens neurons. Opiates directly or indirectly alter the functional activity of the VTA-NAcdopamine system via the different actions of opioid receptors and which could producepositive reinforcement of brain rewarding system or negative effects. The administration of certainneurotrophic factors and transgenic procedures have further highlighted that these opiate-inducedadaptations of the meso-limbic DA system may be the important neural bases of the psychic de-pendence of drug addiction.更多还原