Schilström B, De Villiers S, Malmerfelt A, Svensson T H, Nomikos G G
Karolinska Institutet, Department of Physiology and Pharmacology, Section of Neuropsychopharmacology, Stockholm, Sweden.
Synapse. 2000 Jun 15;36(4):314-21. doi: 10.1002/(SICI)1098-2396(20000615)36:4<314::AID-SYN8>3.0.CO;2-U.
We have previously shown that the nicotine-induced dopamine release in the nucleus accumbens can be attenuated by local administration into the ventral tegmental area (VTA), of antagonists at nicotinic and N-methyl-D-aspartate (NMDA), but not alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. In the present study, we investigated the role of nicotinic and NMDA receptors in the VTA for the expression of Fos-like immunoreactivity (FLI) in the shell and core of the nucleus accumbens and in the medial prefrontal cortex (mPFC) of the rat after acute nicotine administration. Systemically administered nicotine increased FLI in both the mPFC and the nucleus accumbens when compared to saline controls, although this effect was more pronounced, and reached statistical significance in the nucleus accumbens, especially in the core region. When mecamylamine was delivered by reverse dialysis into the VTA, the systemic nicotine-induced FLI was significantly attenuated in the nucleus accumbens. Similarly, the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP-5), infused locally in the VTA, also antagonized the nicotine-induced FLI in the nucleus accumbens. Neither mecamylamine nor AP-5 alone affected basal FLI levels in any of the structures studied. Local administration of nicotine in the VTA increased FLI in the nucleus accumbens but not in the mPFC. Since the nicotine-induced FLI is probably due to an increased dopamine release in both the nucleus accumbens and the mPFC, we conclude that FLI in the nucleus accumbens is mediated, to a large extent, through the activation of dopamine neurons via nicotinic and NMDA receptors in the VTA, whereas the nicotine-induced FLI in the mPFC is subjected to a differential control mechanism, tentatively involving nicotinic receptors at the terminal level of the mPFC-projecting dopamine neurons.
我们之前已经表明，通过向腹侧被盖区（VTA）局部注射烟碱型和N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，但不注射α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）受体拮抗剂，可减弱伏隔核中尼古丁诱导的多巴胺释放。在本研究中，我们调查了急性给予尼古丁后，VTA中的烟碱型和NMDA受体在大鼠伏隔核壳部和核心以及内侧前额叶皮质（mPFC）中Fos样免疫反应性（FLI）表达中的作用。与生理盐水对照组相比，全身给予尼古丁可增加mPFC和伏隔核中的FLI，尽管这种效应在伏隔核中更明显且达到统计学显著性，尤其是在核心区域。当通过反向透析将美加明注入VTA时，全身尼古丁诱导的FLI在伏隔核中显著减弱。同样，局部注入VTA的NMDA受体拮抗剂2-氨基-5-膦酰戊酸（AP-5）也可拮抗尼古丁诱导的伏隔核中的FLI。美加明和AP-5单独使用均未影响所研究的任何结构中的基础FLI水平。在VTA中局部给予尼古丁可增加伏隔核中的FLI，但不增加mPFC中的FLI。由于尼古丁诱导的FLI可能是由于伏隔核和mPFC中多巴胺释放增加所致，我们得出结论，伏隔核中的FLI在很大程度上是通过VTA中的烟碱型和NMDA受体激活多巴胺神经元介导的，而尼古丁诱导的mPFC中的FLI则受到一种不同的控制机制，初步涉及mPFC投射多巴胺神经元终末水平的烟碱型受体。
