多巴胺受体对可卡因诱导的基因表达和MAPK通路激活的调控
发布时间：2019-05-10 21:24
【摘要】：毒品成瘾(drug addiction)指不择手段、不记后果地强制性地获取、使用某种毒品(drug)。毒品成瘾的形成是一个综合性的过程，受多种因素调控，既受心理性、社会性因素影响，也受基因遗传性因素影响。毒品成瘾一旦形成，即可能成为一种终生性的状态。成瘾者不择手段地攫取(crave)毒品，具有极高的复发性(relapse)，甚至在戒断(abstinence)多年后仍有可能复发(relapse)，造成很大的社会问题。毒品成瘾的形成是一个循序渐进的过程，在此过程，机体在分子、细胞学水平发生了代偿性变化，进而导致成瘾的一系列症状。毒品成瘾的核心问题是长期使用成瘾药物后，中枢神经系统产生可塑性变化，而这种可塑性变化的基础是基因和分子水平的变化。 业已证明，包括阿片类、可卡因在内的多种毒品成瘾的共同神经生物学特点是激活多巴胺系统。迄今，已克隆出5种多巴胺受体，分为两大类：D1类和D2类。D1类受体包括D1和D5受体，而D2类受体包括D2、D3和D4受体。D1多巴胺受体是体内分布最广泛的受体，主要分布于纹状体、NAc与嗅球，同时在边缘系统、下丘脑与丘脑中也有表达。D3多巴胺受体主要分布于伏核(nucleus accumbens，NAc)，嗅球与Calleja岛，同时在尾壳核(caudoputamen，CPu)也有一定的表达。D2多巴胺受体的分布与D1类似，，而D4和D5多巴胺受体在体内的表达很低。阿片类、可卡因等毒品通过多巴胺受体影响细胞内信号传导通路，而影响基因的表达，这些基因表达的变化参与神经元可塑性(neuron
[Abstract]:Drug addiction (drug addiction) refers to the compulsory acquisition, regardless of the consequences, of the use of some kind of drug, (drug)., by any means, without regard to the consequences. The formation of drug addiction is a comprehensive process, which is regulated by many factors, not only by psychological and social factors, but also by genetic factors. Once drug addiction is formed, it may become an end-of-life state. Addicts seize (crave) drugs by any means, and have a very high level of recurrent (relapse), which may still cause great social problems even after abstinence from (abstinence) for many years. The formation of drug addiction is a gradual process, in which the body has undergone compensated changes at the molecular and cellular levels, which leads to a series of symptoms of addiction. The core problem of drug addiction is that after long-term use of addictive drugs, the central nervous system produces plastic changes, which are based on changes in gene and molecular levels. Common neurobiological characteristics of drug addiction, including opioids and cocaine, have proven to be the activation of the dopamine system. So far, five dopamine receptors have been cloned and divided into two categories: D1 and D2. D1 receptors include D1 and D5 receptors, while D2 receptors include D2, D2 and D4 receptors. D1 dopamine receptors are the most widely distributed receptors in vivo. It is mainly distributed in striatum, NAc and olfactory bulb, and is also expressed in limbic system, Hypothalamus and thalamus. D 3 dopamine receptor is mainly distributed in nucleus accumbens (nucleus accumbens,NAc), olfactory bulb and Calleja island, as well as in putamen tail putamen (caudoputamen,). The distribution of D2 dopamine receptors was similar to that of D1, while the expression of D4 and D5 dopamine receptors was very low in vivo. Opioids, cocaine and other drugs affect intracellular signal transduction pathway and gene expression through dopamine receptors. The changes of these gene expression are involved in neuronal plasticity (neuron).
【学位授予单位】：第一军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392
本文编号：2474007
[Abstract]:Drug addiction (drug addiction) refers to the compulsory acquisition, regardless of the consequences, of the use of some kind of drug, (drug)., by any means, without regard to the consequences. The formation of drug addiction is a comprehensive process, which is regulated by many factors, not only by psychological and social factors, but also by genetic factors. Once drug addiction is formed, it may become an end-of-life state. Addicts seize (crave) drugs by any means, and have a very high level of recurrent (relapse), which may still cause great social problems even after abstinence from (abstinence) for many years. The formation of drug addiction is a gradual process, in which the body has undergone compensated changes at the molecular and cellular levels, which leads to a series of symptoms of addiction. The core problem of drug addiction is that after long-term use of addictive drugs, the central nervous system produces plastic changes, which are based on changes in gene and molecular levels. Common neurobiological characteristics of drug addiction, including opioids and cocaine, have proven to be the activation of the dopamine system. So far, five dopamine receptors have been cloned and divided into two categories: D1 and D2. D1 receptors include D1 and D5 receptors, while D2 receptors include D2, D2 and D4 receptors. D1 dopamine receptors are the most widely distributed receptors in vivo. It is mainly distributed in striatum, NAc and olfactory bulb, and is also expressed in limbic system, Hypothalamus and thalamus. D 3 dopamine receptor is mainly distributed in nucleus accumbens (nucleus accumbens,NAc), olfactory bulb and Calleja island, as well as in putamen tail putamen (caudoputamen,). The distribution of D2 dopamine receptors was similar to that of D1, while the expression of D4 and D5 dopamine receptors was very low in vivo. Opioids, cocaine and other drugs affect intracellular signal transduction pathway and gene expression through dopamine receptors. The changes of these gene expression are involved in neuronal plasticity (neuron).
【学位授予单位】：第一军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392
【引证文献】
相关博士学位论文 前1条
1 任二军;蓝狐自咬症及遗传学基础研究[D];中国农业科学院;2011年
本文编号：2474007
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