The Role of the Habenula in Nicotine Addiction.
The Role of the Habenula in Nicotine Addiction.
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DOI：
10.4172/2155-6105.s1-002
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发表时间：
2011
期刊：
影响因子：
--
通讯作者：
P. Baldwin;Raul Alanis;R. Salas
中科院分区：
文献类型：
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作者：
P. Baldwin;Raul Alanis;R. Salas
为了在任何特定的环境中茁壮成长，移动的生物必须能够从成功和失败的事件中学习。为了从成功中学习，大脑依赖于源自腹侧被盖区和黑质的信号，这些信号导致纹状体中多巴胺的释放增加。最近，研究表明，从失望中学习，大脑依赖于源自外侧缰的信号，这间接抑制了多巴胺能活动。缰核是一个小的大脑区域，在小鼠中被证明对尼古丁戒断症状的出现至关重要。内侧缰表达的烟碱乙酰胆碱受体亚单位是观察小鼠戒断症状所必需的，仅阻断内侧缰中的烟碱活性就足以促使依赖性小鼠戒断。此外，最近的全基因组关联研究表明，在人类中，相同烟碱受体亚基中的遗传变异至少部分导致成为吸烟者的遗传倾向。缰不仅与尼古丁有关，还与其他几种药物的作用有关。我们推测，持续使用滥用药物的结果在缰过度活跃作为一种补偿机制，人为升高多巴胺的释放。然后，药物戒断会导致非代偿性的缰核过度活动，并且可以被认为是一种持续的失望状态（或消极的情绪状态），从而导致重复使用药物。我们相信，改变缰核活动的药物可能是治疗吸烟和药物成瘾的有效方法。
To thrive in any given environment, mobile creatures must be able to learn from the outcomes of both successful and disappointing events. To learn from success, the brain relies on signals originating in the ventral tegmental area and substantia nigra that result in increased release of dopamine in the striatum. Recently, it was shown that to learn from disappointment the brain relies on signals originating in the lateral habenula, which indirectly inhibit dopaminergic activity. The habenula is a small brain region that has been shown in mice to be critical for the appearance of nicotine withdrawal symptoms. The nicotinic acetylcholine receptor subunits expressed in the medial habenula are necessary to observe withdrawal symptoms in mice, and blocking nicotinic activity in the medial habenula only is sufficient to precipitate withdrawal in dependent mice. In addition, recent genome wide association studies have shown that in humans, genetic variants in the same nicotinic receptor subunits are at least partially responsible for the genetic predisposition to become a smoker. The habenula is linked not only to nicotine, but also to the effects of several other drugs. We postulate that the continuous use of drugs of abuse results in habenular hyperactivity as a compensatory mechanism for artificially elevated dopamine release. Drug withdrawal would then result in non-compensated habenular hyperactivity, and could be thought of as a state of continuous disappointment (or a negative emotional state), driving repeated drug use. We believe that drugs that alter habenular activity may be effective therapies against tobacco smoke and drug addiction in general.