尼古丁成瘾
中文名称
通路描述
尼古丁是烟草中主要的精神活性成分之一，有助于有害的吸烟习惯。成瘾药物（包括尼古丁）的一个共同特征是它们会增加纹状体（NAc）中的多巴胺（DA）释放。主要投射到NAc的突触前神经元位于腹侧被盖区（VTA）。在VTA中，含有alpha6和alpha4beta2亚型的烟碱型乙酰胆碱受体（nAChRs）位于GABA能突触末梢，提供对DA能神经元的抑制性输入，而含有alpha7亚型的nAChRs位于谷氨酸能突触上，这些受体的激活增强谷氨酸释放并增加DA能神经元的兴奋性。尼古丁作为激动剂激活并脱敏这些烟碱型乙酰胆碱受体（nAChRs）。在尼古丁的短暂暴露后，位于GABA能突触上的alpha6*和alpha4beta2* nAChRs脱敏，降低GABA释放并降低对DA神经元的局部抑制。但是，位于谷氨酸能突触上的alpha7* nAChRs保持活跃，增强谷氨酸对DA神经元的兴奋性，导致NAc中DA释放增加，从而促进尼古丁的奖赏效应。
英文描述
Nicotine is one of the main psychoactive ingredients in tobacco that contributes to the harmful tobacco smoking habit. A common feature of addictive drugs, including nicotine, is that they increase dopamine (DA) release in the nucleus accumbens (NAc). The principal dopaminergic projections to NAc arise from neurons in the ventral tegmental area (VTA). In the VTA, alpha6- and alpha4beta2-containing nAChRs (alpha6*-AChRs and alpha4beta2*-AChRs, respectively) are located on GABAergic terminals and provide inhibitory inputs onto DAergic neuons, while alpha7*-nAChRs are located on glutamatergic terminals and activation of these receptors enhances glutamate release and increases excitability of DAergic neurons. Nicotine acts as an agonist to activate and desensitize these nicotinic acetylcholine receptors (nAChRs). After a short exposure to nicotine, alpha6*- and alpha4beta2*- nAChRs on GABAergic afferents are desensitized, decreasing GABA release and decreasing local inhibition of DA neurons. But the alpha7*-nAChRs on glutamatergic afferents remain active and enhance glutamate excitation of the DA neurons, leading to increased DA release in the NAc -and so facilitate the reinforcing effects of nicotine.
所含基因
41 个基因