Schilström B, Svensson H M, Svensson T H, Nomikos G G
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Neuroscience. 1998 Aug;85(4):1005-9. doi: 10.1016/s0306-4522(98)00114-6.
We have recently shown that the stimulatory effect of nicotine on dopamine output in the nucleus accumbens is largely dependent upon an enhanced glutamate transmission via N-methyl-D-aspartate receptors, possibly through stimulation of nicotinic receptors localized presynaptically on glutamatergic afferents in the ventral tegmental area. Given that nicotinic alpha7 receptors have been proposed to be involved in presynaptic regulation of glutamate release, we investigated whether alpha7 receptors underlie such a mechanism in the ventral tegmental area. For this purpose, by utilizing microdialysis we measured dopamine release in the nucleus accumbens in response to systemic nicotine, with, or without, concomitant infusion into the ventral tegmental area of the selective alpha7 receptor antagonist methyllycaconitine. To test also whether alpha7 nicotinic receptor antagonism within the ventral tegmental area affected a natural reward-mediated increase in dopamine release in the nucleus accumbens, we employed a model of schedule-induced feeding. Intrategmental administration of methyllycaconitine decreased both the nicotine-induced and the food-induced dopamine release in the nucleus accumbens. We suggest that alpha7 nicotinic receptors in the ventral tegmental area are involved in the acute effect of nicotine on dopamine release in the nucleus accumbens and conclude that the mechanism, by which nicotine stimulates the mesolimbic dopaminergic system, may be an essential constituent of the natural reward-related circuits in brain.
我们最近发现，尼古丁对伏隔核中多巴胺释放的刺激作用很大程度上依赖于通过N-甲基-D-天冬氨酸受体增强的谷氨酸传递，这可能是通过刺激腹侧被盖区谷氨酸能传入神经突触前定位的烟碱样受体实现的。鉴于烟碱样α7受体被认为参与谷氨酸释放的突触前调节，我们研究了α7受体是否是腹侧被盖区这种机制的基础。为此，我们利用微透析技术，测量了在有或没有向腹侧被盖区同时注入选择性α7受体拮抗剂甲基lycaconitine的情况下，系统给予尼古丁后伏隔核中多巴胺的释放。为了测试腹侧被盖区内α7烟碱样受体拮抗作用是否也会影响伏隔核中自然奖赏介导的多巴胺释放增加，我们采用了定时诱导进食模型。在腹侧被盖区内给予甲基lycaconitine可降低尼古丁诱导的和食物诱导的伏隔核中多巴胺的释放。我们认为腹侧被盖区的α7烟碱样受体参与了尼古丁对伏隔核中多巴胺释放的急性作用，并得出结论，尼古丁刺激中脑边缘多巴胺能系统的机制可能是大脑中与自然奖赏相关回路的重要组成部分。
