Pogun S, Demirgoren S, Taskiran D, Kanit L, Yilmaz O, Koylu E O, Balkan B, London E D
Ege University Center for Brain Research and TUBITAK Basic Neuroscience Research Unit, 35100, Izmir, Turkey.
Eur Neuropsychopharmacol. 2000 Dec;10(6):463-72. doi: 10.1016/s0924-977x(00)00116-4.
Nicotine exerts its central actions by regulating cationic fluxes through nicotinic acetylcholine receptors (nAChRs). By this effect, the drug likely also modifies events occurring beyond the nAChR, including the regulation of nitric oxide (NO) synthesis. The present study was undertaken to assess the effects of acute and chronic nicotine administration (0.4 mg/kg, s.c.) on levels of NO(-)(2)+NO(-)(3), stable metabolites of NO, in brain regions of male and female rats. Nicotine increased levels of the metabolites, and therefore presumably of NO, with sex differences in the degree of stimulation, the brain regions affected, and the variance between the effects of acute and chronic administration. Prior inhibition of NO synthase eliminated the effect of nicotine in all regions studied. While nicotine appeared to increase NO indirectly via glutamate receptors in the cortex and hippocampus, this was not true of the corpus striatum, where blocking NMDA-type glutamate receptors with MK-801 had no effect. The findings support the view that NO is likely involved in some of the central effects of nicotine.
尼古丁通过调节阳离子通过烟碱型乙酰胆碱受体（nAChRs）的通量来发挥其中枢作用。通过这种作用，该药物可能还会改变nAChR以外发生的事件，包括一氧化氮（NO）合成的调节。本研究旨在评估急性和慢性给予尼古丁（0.4mg/kg，皮下注射）对雄性和雌性大鼠脑区中NO（-）（2）+NO（-）（3）（NO的稳定代谢产物）水平的影响。尼古丁增加了代谢产物的水平，因此推测也增加了NO的水平，在刺激程度、受影响的脑区以及急性和慢性给药效果之间的差异方面存在性别差异。预先抑制一氧化氮合酶消除了尼古丁在所研究的所有区域中的作用。虽然尼古丁似乎通过皮质和海马体中的谷氨酸受体间接增加NO，但纹状体并非如此，用MK-801阻断NMDA型谷氨酸受体对纹状体没有影响。这些发现支持了NO可能参与尼古丁某些中枢作用的观点。
