Dani John A, Jenson Daniel, Broussard John I, De Biasi Mariella
Department of Neuroscience, Center on Addiction, Learning, Memory, Baylor College of Medicine, Houston, Texas 77030-3498, USA.
J Addict Res Ther. 2011 Apr 20;S1(1). doi: 10.4172/2155-6105.S1-001.
Tobacco use is a major health problem, and nicotine is the main addictive component. Nicotine binds to nicotinic acetylcholine receptors (nAChR) to produce its initial effects. The nAChRs subtypes are composed of five subunits that can form in numerous combinations with varied functional and pharmacological characteristics. Diverse psychopharmacological effects contribute to the overall process of nicotine addiction, but two general neural systems are emerging as critical for the initiation and maintenance of tobacco use. Mesocorticolimbic circuitry that includes the dopaminergic pathway originating in the ventral tegmental area and projecting to the nucleus accumbens is recognized as vital for reinforcing behaviors during the initiation of nicotine addiction. In this neural system β2, α4, and α6 are the most important nAChR subunits underlying the rewarding aspects of nicotine and nicotine self-administration. On the other hand, the epithalamic habenular complex and the interpeduncular nucleus, which are connected via the fasciculus retroflexus, are critical contributors regulating nicotine dosing and withdrawal symptoms. In this case, the α5 and β4 nAChR subunits have critical roles in combination with other subunits. In both of these neural systems, particular nAChR subtypes have roles that contribute to the overall nicotine addiction process.
吸烟是一个主要的健康问题，而尼古丁是主要的成瘾成分。尼古丁与烟碱型乙酰胆碱受体（nAChR）结合以产生其初始效应。nAChR亚型由五个亚基组成，这些亚基可以以多种组合形式形成，具有不同的功能和药理学特性。多种精神药理学效应促成了尼古丁成瘾的整个过程，但两个主要的神经系统正逐渐被认为对吸烟行为的起始和维持至关重要。包括起源于腹侧被盖区并投射到伏隔核的多巴胺能通路在内的中脑边缘叶回路被认为在尼古丁成瘾起始过程中的强化行为中至关重要。在这个神经系统中，β2、α4和α6是尼古丁奖励方面和尼古丁自我给药背后最重要的nAChR亚基。另一方面，通过后屈束相连的上丘脑缰核复合体和脚间核是调节尼古丁剂量和戒断症状的关键因素。在这种情况下，α5和β4 nAChR亚基与其他亚基结合发挥关键作用。在这两个神经系统中，特定的nAChR亚型都对尼古丁成瘾的整个过程发挥作用。
