The putative role of extra-synaptic mesolimbic dopamine in the neurobiology of nicotine dependence
The putative role of extra-synaptic mesolimbic dopamine in the neurobiology of nicotine dependence
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DOI：
10.1016/s0166-4328(00)00202-3
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发表时间：
2000-08-01
影响因子：
2.7
通讯作者：
Birrell, CE
中科院分区：
文献类型：
--
作者：
Balfour, DJK;Wright, AE;Birrell, CE
大多数习惯性吸烟者发现很难戒掉这个习惯，因为他们对烟草烟雾中的尼古丁上瘾。尼古丁，像其他滥用的精神兴奋剂药物一样，增加了中脑边缘系统的主要终端领域多巴胺的释放，有证据表明，这介导了药物的“奖励”特性，这加强了其自我管理。这篇评论的重点是工作的假设，尼古丁成瘾，和其他精神兴奋剂药物，取决于他们的能力，以引起持续增加多巴胺释放直接进入细胞外的空间，位于细胞之间的细胞在丘脑核，在那里它刺激突触外多巴胺受体。有人建议，这些受体的刺激增加与增加激励学习或增加的激励显着性与收购和交付的药物相关的线索的属性。该假说提出，这些线索可以成为吸毒行为的条件反射。这些受体介导尼古丁对中脑多巴胺神经元的作用，通过持续暴露于习惯性吸烟者血浆中常见浓度的尼古丁而脱敏。有人提出，当血浆尼古丁浓度高到足以引起受体脱敏时，烟草烟雾中存在的条件尼古丁维持了吸烟。因此，该假说预测，条件强化可能在烟草成瘾中发挥比大多数其他成瘾行为更重要的作用。因此，对尼古丁的研究有可能有助于我们理解成瘾的神经生物学，而这是不容易用可卡因和安非他明等药物来探索的，这些药物总是会增加前脑中的多巴胺溢出。(C)2000 Elsevier Science B.V.保留所有权利。
A majority of habitual tobacco smokers find it very difficult to quit the habit because they become addicted to the nicotine present in tobacco smoke. Nicotine, like other psychostimulant drugs of abuse, increases dopamine release in the principal terminal field of the mesolimbic system, the nucleus accumbens, and there is evidence that this mediates the 'rewarding' properties of the drug, which reinforce its self-administration. This review focuses on the working hypothesis that addiction to nicotine, and other psychostimulant drugs, depends upon their ability to evoke a sustained increase in dopamine release directly into the extracellular space which lies between the cells in the nucleus accumbens where it stimulates extra-synaptic dopamine receptors. It is suggested that increased stimulation of these receptors is associated with increased incentive learning or the attribution of increased incentive salience to the cues associated with acquisition and delivery of the drug. The hypothesis proposes that these cues can become conditioned reinforcers of drug-taking behaviour. The receptors, which mediate the effects of nicotine on mesoaccumbens dopamine neurones, are desensitised by sustained exposure to nicotine at concentrations commonly found in the plasma of habitual smokers. It is proposed that, at times when the plasma nicotine concentration is sufficiently high to cause desensitisation of the receptors, tobacco smoking is maintained by the conditioned reinforcers present in the tobacco smoke. The hypothesis predicts, therefore, that conditioned reinforcement may play a more important role in the addiction to tobacco than for most other addictive behaviours. As a result, studies with nicotine have the potential to contribute to our understanding of the neurobiology of addiction which cannot easily be explored using drugs, such as cocaine and amphetamine, which invariably increase dopamine overflow in the forebrain. (C) 2000 Elsevier Science B.V. All rights reserved.