Kiba H, Jayaraman A
Department of Neurology, LSU School of Medicine, New Orleans 70112.
Brain Res Mol Brain Res. 1994 Apr;23(1-2):1-13. doi: 10.1016/0169-328x(94)90205-4.
The powerful psychostimulant and positive reinforcing effects of nicotine have been speculated to be mediated by the dopaminergic neurons of the ventral tegemental area (VTA) and their terminals in the nucleus accumbens. To extend our understanding of nicotine and dopamine interactions, we mapped the pattern of c-fos expression in the striatum as an important marker of some of the earliest changes that occur at gene transcription level. Acute nicotine injections in rats led to Fos expression more prominently in the caudatoputamen than in the nucleus accumbens in a dose-dependent fashion. Fos-reactive cells were more prominent in the central and dorsomedial limbic caudatoputamen than in the dorsolateral sensory-motor striatum. Injections of mecamylamine completely blocked nicotine-induced Fos expression. Injections of the selective dopamine D1 antagonist SCH 23390, but not D2 antagonist YM 09151-2 or Clozapine, a drug with high affinity to D4 receptors, before nicotine injections, completely blocked Fos expression in the striatum. Nicotine induced Fos expression was also blocked completely by the NMDA receptor antagonists MK-801 and CPP. These results suggest that nicotine-induced Fos expression in the striatum is mediated mostly by dopamine D1 receptors and that the Fos expression is also dependent on N-methyl-D-aspartate (NMDA) stimulation.
尼古丁强大的精神兴奋和正向强化作用被推测是由腹侧被盖区（VTA）的多巴胺能神经元及其在伏隔核的终末介导的。为了拓展我们对尼古丁与多巴胺相互作用的理解，我们将纹状体中c-fos表达模式作为在基因转录水平发生的一些最早变化的重要标志物进行了定位。给大鼠急性注射尼古丁后，尾壳核中Fos表达比伏隔核更显著，且呈剂量依赖性。Fos反应性细胞在中央和背内侧边缘尾壳核中比在背外侧感觉运动纹状体中更突出。注射美加明可完全阻断尼古丁诱导的Fos表达。在注射尼古丁前注射选择性多巴胺D1拮抗剂SCH 23390，而非D2拮抗剂YM 09151-2或对D4受体具有高亲和力的药物氯氮平，可完全阻断纹状体中的Fos表达。尼古丁诱导的Fos表达也被NMDA受体拮抗剂MK-801和CPP完全阻断。这些结果表明，尼古丁诱导的纹状体Fos表达主要由多巴胺D1受体介导，且Fos表达也依赖于N-甲基-D-天冬氨酸（NMDA）刺激。
