Mansvelder Huibert D, De Rover Mischa, McGehee Daniel S, Brussaard Arjen B
Department of Experimental Neurophysiology, Institute for Neurosciences and Centre for Neurogenomics and Cognitive Research, Vrije Universiteit Amsterdam, de Boelelaan 1087, 1081 HV, Amsterdam, The Netherlands.
Eur J Pharmacol. 2003 Nov 7;480(1-3):117-23. doi: 10.1016/j.ejphar.2003.08.099.
Nicotine reinforces smoking behaviour by activating nicotinic acetylcholine receptors in the midbrain dopaminergic reward centres. Upstream of the dopaminergic neurons nicotine induces long-term potentiation of the excitatory input to dopamine cells in the ventral tegmental area, and depresses inhibitory inputs. Both effects of nicotine were shown to last much longer than the nicotine exposure and together will activate the dopaminergic ventral tegmental area projection toward the nucleus accumbens. However, downstream of dopamine, effects of nicotine are also likely to occur. Cholinergic interneurons within the nucleus accumbens are important in the tonic control of the gamma-amino buteric acid (GABA) nucleus accumbens output neurons, which project back to the ventral tegmental area. The nicotinic acetylcholine receptors that mediate this control are likely to desensitise upon preexposure to the nicotine concentrations found in the blood of smokers. Thus, synaptic mechanisms both upstream and downstream of dopamine release are potentially important factors contributing to the etiology of nicotine addiction.
尼古丁通过激活中脑多巴胺能奖赏中枢的烟碱型乙酰胆碱受体来强化吸烟行为。在多巴胺能神经元的上游，尼古丁可诱导腹侧被盖区多巴胺细胞兴奋性输入的长期增强，并抑制抑制性输入。尼古丁的这两种作用都比尼古丁暴露持续的时间长得多，并且共同激活多巴胺能腹侧被盖区向伏隔核的投射。然而，在多巴胺的下游，尼古丁的作用也可能会发生。伏隔核内的胆碱能中间神经元在对γ-氨基丁酸（GABA）伏隔核输出神经元的紧张性控制中很重要，这些输出神经元会投射回腹侧被盖区。介导这种控制的烟碱型乙酰胆碱受体在预先暴露于吸烟者血液中发现的尼古丁浓度后可能会脱敏。因此，多巴胺释放上游和下游的突触机制都是导致尼古丁成瘾病因的潜在重要因素。
