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药物成瘾的神经基础

Neural Basis of Drug Addiction
课程网址: http://videolectures.net/mitworld_everitt_nbda/  
主讲教师: Barry Everitt
开课单位: 剑桥大学
开课时间: 2010-08-09
课程语种: 英语
中文简介:
有人如何从娱乐用药转向成瘾?剑桥大学的Barry Everitt小组一直试图以极高的精确度打破成瘾的阶段和神经回路.Everitt的研究试图将动物的进展从自愿服用药物,到获得的吸毒习惯,到强迫性药物寻求和消费的阶段,“个体真正失去控制的地方。”这种进展似乎植根于大脑中不同学习系统的顺序激活,这些系统对神经递质多巴胺特别敏感。研究表明吸毒最初是依赖于伏隔核(腹侧纹状体的一部分),但其建立涉及背侧纹状体。研究表明,背侧纹状体中的多巴胺与大鼠寻找药物的行为有因果关系。随着动物习惯服用可卡因,“从腹侧到背侧纹状体的联合编码平衡发生了转变。”可卡因的渴望和自我管理似乎也改变了猴子和人类背侧纹状体的功能。虽然这样做了。从腹侧到背侧纹状体的转变在某种程度上取决于“药理学”(可卡因对多巴胺能系统的影响),Everitt假设它还可能涉及连接腹侧纹状体,中脑,大脑的动机和运动机制以及背侧的“螺旋形电路”。纹状体。埃弗里特推测,药物寻求的强迫性可能部分源于前额叶皮层,这是“自上而下的执行控制机制”的所在地。他描述了试图模拟这种强迫的研究。短期可获得可卡因的动物和长期接触可卡因的大多数动物在受到惩罚时会抑制其寻求药物的反应。但是,20%的一个小组“在面对惩罚时仍然坚持寻求可卡因。”这一结果现在已被多次复制,并且在人类之间存在着相似之处。埃弗里特说,这引起了药物成瘾的脆弱性问题。“另外的研究表明,冲动性是一种”行为特征,可以预测从最初的药物摄入到失去控制......到强迫性寻求和服用“药物的过渡。高度冲动的动物否认可卡因随着时间的推移变得更加冲动和吸毒,导致复发。埃弗里特和其他人正在追踪强迫性前额皮质损伤的神经基础,这涉及长期吸毒后建立的“失去对适应不良习惯的控制”。
课程简介: How does someone move from recreational drug use to addiction? Barry Everitt’s group at the University of Cambridge has been trying to break down the stages and neural circuitry of addiction with great precision. Everitt’s research attempts to operationalize a progression in animals from the voluntary taking of drugs, to the acquired habit of drug-taking, to the stage of compulsive drug-seeking and consumption, “where individuals have really lost control.” This progression seems rooted in the sequential activation of different learning systems in the brain, which are particularly sensitive to the neurotransmitter dopamine. Research suggests that drug-taking is initially dependent on the nucleus accumbens (part of the ventral striatum), but its establishment involves the dorsal striatum. Studies show that dopamine in the dorsal striatum is causally involved in establishing drug-seeking behavior in rats. As the animal gets accustomed to taking the cocaine, there’s a “shift in the balance of associative encoding from ventral to dorsal striatum.” Cocaine craving and self-administration seem to change the functioning of the dorsal striatum in monkeys and humans as well. While this shift from ventral to dorsal striatum depends to some degree on “pharmacology” (cocaine’s impact on dopaminergic systems), Everitt has hypothesized that it may also involve “spiraling circuitry” connecting the ventral striatum, the midbrain -- the brain’s motivational and motor mechanisms -- and the dorsal striatum. Everitt speculates that the compulsive nature of drug seeking may be rooted in part in the prefrontal cortex, home to “top-down executive control mechanisms.” He describes research that attempted to model this type of compulsion. Animals with short-term access to cocaine and most animals with long-term access to cocaine suppressed their drug-seeking responses when punished. But a subgroup of 20% “persisted in seeking cocaine in the face of punishment.” This result has been replicated many times now, and turns out to have a parallel among humans. This, says Everitt, “brings up the issue of vulnerability to drug addiction.” Additional research suggests that impulsivity is a “behavioral characteristic that predicts the transition from initial drug intake to loss of control … to compulsive seeking and taking” of drugs. Highly impulsive animals denied cocaine become more impulsive and drug seeking over time, leading to relapses. Everitt and others are tracing the neural basis of compulsivity to impairment in the prefrontal cortex, which involves “a loss of control over maladaptive habits” established after long-term drug taking.
关 键 词: 多巴胺; 伏隔核; 吸毒
课程来源: 视频讲座网
最后编审: 2019-05-29:lxf
阅读次数: 114