NEURAL MECHANISMS UNDERLYING NICOTINE DEPENDENCE
NEURAL MECHANISMS UNDERLYING NICOTINE DEPENDENCE
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DOI：
10.1111/j.1360-0443.1994.tb03738.x
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发表时间：
1994-11-01
期刊：
影响因子：
6
通讯作者：
BALFOUR, DJK
中科院分区：
文献类型：
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作者：
BALFOUR, DJK
毫无疑问，许多习惯性吸烟者发现很难戒掉这个习惯，因为他们已经对烟雾中的尼古丁上瘾了。本文讨论了这种成瘾的一些药理学机制，并讨论了如何了解这些机制可能有助于更有效地使用尼古丁替代疗法戒烟。它批判性地考虑了尼古丁的“奖励”特性的证据，这种特性有助于加强药物寻求行为，与大脑中脑边缘多巴胺系统的刺激有关。批评特别集中在许多中枢烟碱受体的证据，包括那些介导药物对多巴胺分泌的影响，很容易通过长期暴露于激动剂而脱敏，假设从烟草烟雾中吸入的尼古丁总是导致受体刺激必须谨慎对待。然而，大脑中的烟碱受体本质上是异质的，具有不同的分子结构和药理学。它的结论是，吸烟者寻求尼古丁的增强性能可能反映了不同的烟碱受体群体的刺激和脱敏，吸烟者可以调整他们的吸烟习惯，以实现平衡的受体刺激和脱敏，他们发现最增强。不同尼古丁制剂在戒烟治疗期间的疗效似乎也可能反映了它们刺激或脱敏大脑尼古丁受体的能力。
There is little doubt that many habitual smokers find it difficult to quit the habit because they have become addicted to the nicotine present in the smoke. This paper addresses some of the pharmacological mechanisms underlying this addiction and discusses how an understanding of these mechanisms may contribute to the more effective use of nicotine replacement therapy during smoking cessation. It considers critically the evidence that the ''rewarding'' properties of nicotine, which serve to reinforce drug-seeking behaviour, are related to stimulation of the mesolimbic dopamine system of the brain. The critique focuses specifically on the evidence that many central nicotinic receptors, including those which mediate the effects of the drug on dopamine secretion, are readily desensitized by chronic exposure to agonist and that hypotheses which assume that nicotine inhaled from tobacco smoke invariably results in stimulation of the receptors must be treated with caution. Nicotinic receptors in the brain are, however, heterogeneous in nature with different molecular structures and pharmacologies. It is concluded that the reinforcing properties of nicotine sought by smokers may reflect both stimulation and desensitization of the different nicotinic receptor populations, and that smokers may adjust their smoking habits to achieve the balance of receptor stimulation and desensitization which they find most reinforcing. It seems likely that the efficacy of the different nicotine formulations during the treatment of smoking cessation may also reflect their ability to stimulate or desensitize brain nicotinic receptors.