Bean A J, During M J, Deutch A Y, Roth R H
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
J Neurosci. 1989 Dec;9(12):4430-8. doi: 10.1523/JNEUROSCI.09-12-04430.1989.
Interactions between striatal dopamine (DA) and neurotensin (NT) have been suggested by anatomical, behavioral, and biochemical studies. Nigrostriatal DA neurons, in contrast to mesocorticolimbic DA neurons, do not appear to contain NT. Thus, distinct neuronal elements subserve interactions between DA and NT within the striatum. We have previously demonstrated that reserpine-induced depletion of striatal DA is accompanied by a dose- and time-dependent increase in striatal NT concentrations. In order to further characterize the effects of reserpine and to define the mechanism by which reserpine acts to increase striatal NT concentrations, we have used immunohistochemical and biochemical approaches. Immunohistochemical examination of rats pretreated with reserpine revealed marked increases in the density of NT-like immunoreactive (NT-li) perikarya and fibers, and the development of NT-li patches. Pretreatment with reserpine had no apparent effect on NT synthesis, as assessed by examination of cycloheximide-induced inhibition of protein synthesis. However, reserpine administration resulted in a significant decrease in the release of both DA and NT into the striatal extracellular fluid, as measured by in vivo microdialysis. These data suggest that the increase in striatal NT concentrations observed after reserpine treatment results from decreased release, rather than increased synthesis of the peptide.
解剖学、行为学和生物化学研究表明，纹状体多巴胺（DA）与神经降压素（NT）之间存在相互作用。与中脑皮质边缘多巴胺神经元不同，黑质纹状体多巴胺神经元似乎不含有神经降压素。因此，不同的神经元成分参与纹状体内多巴胺与神经降压素之间的相互作用。我们之前已经证明，利血平诱导的纹状体多巴胺耗竭伴随着纹状体神经降压素浓度的剂量和时间依赖性增加。为了进一步表征利血平的作用并确定利血平增加纹状体神经降压素浓度的作用机制，我们采用了免疫组织化学和生物化学方法。对用利血平预处理的大鼠进行免疫组织化学检查发现，神经降压素样免疫反应性（NT-li）胞体和纤维的密度显著增加，并且出现了NT-li斑块。通过检查环己酰亚胺诱导的蛋白质合成抑制来评估，利血平预处理对神经降压素合成没有明显影响。然而，通过体内微透析测量，给予利血平导致多巴胺和神经降压素向纹状体细胞外液的释放显著减少。这些数据表明，利血平治疗后观察到的纹状体神经降压素浓度增加是由于释放减少，而不是该肽的合成增加。
