Szigethy E, Beaudet A
Montreal Neurological Institute, McGill University, Quebec, Canada.
J Comp Neurol. 1989 Jan 1;279(1):128-37. doi: 10.1002/cne.902790111.
Several lines of anatomical, biochemical, and pharmacological evidence have suggested that specific high affinity neurotensin binding sites are associated with dopamine-containing neurons in the rat ventral tegmentum. In the present study we confirmed and quantified the extent of this association by combining monoiodinated neurotensin radioautography and tyrosine hydroxylase immunohistochemistry on adjacent 5-10 microns-thick midbrain sections. We found that 95-100% tyrosine hydroxylase-immunoreactive neurons detected in all subdivisions of the substantia nigra (pars compacta, pars lateralis, and pars reticulata) exhibited intense 125I-neurotensin labeling in adjacent light microscopic radioautographs. Tyrosine hydroxylase-positive dendrites radiating downward from compacta neurons were also heavily labeled throughout the pars reticulata. In the paranigral subdivision of the ventral tegmental area, silver grains were evenly distributed over neuropil and perikarya and therefore could not be readily attributed to any given tyrosine hydroxylase-positive element. In contrast, within the parabrachial pigmentous subdivision of the ventral tegmental area, 80-90% of the tyrosine hydroxylase-immunoreactive somata and proximal processes were clearly in register with 125I-neurotensin labeled cells. Finally, all tightly packed TH-positive neurons in the interfascicular nucleus showed intense 125I-neurotensin labeling. The vast majority of the neurotensin binding sites observed in the ventral midbrain tegmentum were of the high affinity, physiologically active receptor type since levocabastine, a selective blocker of the low affinity neurotensin binding component, had minimal effect on the binding density in any of the midbrain regions examined. The present results demonstrate an extensive overlap between specific, high affinity neurotensin binding sites and dopamine perikarya and dendrites in the rat ventral tegmentum, and thereby provide a direct anatomical substrate for observed neurotensin-dopamine interactions in the mesocorticolimbic and nigrostriatal projection systems.
多条解剖学、生物化学和药理学证据表明，特定的高亲和力神经降压素结合位点与大鼠腹侧被盖区含多巴胺的神经元相关。在本研究中，我们通过对相邻的5 - 10微米厚的中脑切片进行单碘化神经降压素放射自显影和酪氨酸羟化酶免疫组织化学相结合的方法，证实并量化了这种关联的程度。我们发现，在黑质的所有亚区（致密部、外侧部和网状部）检测到的95 - 100%的酪氨酸羟化酶免疫反应性神经元，在相邻的光学显微镜放射自显影片中显示出强烈的125I - 神经降压素标记。从致密部神经元向下辐射的酪氨酸羟化酶阳性树突在整个网状部也被大量标记。在腹侧被盖区的黑质旁亚区，银粒均匀分布在神经毡和胞体上，因此不易归因于任何特定的酪氨酸羟化酶阳性成分。相比之下，在腹侧被盖区的臂旁色素亚区内，80 - 90%的酪氨酸羟化酶免疫反应性胞体和近端突起与125I - 神经降压素标记的细胞明显对齐。最后，束间核中所有紧密排列的TH阳性神经元都显示出强烈的125I - 神经降压素标记。在腹侧中脑被盖区观察到的绝大多数神经降压素结合位点是高亲和力、生理活性受体类型，因为左卡巴斯汀是低亲和力神经降压素结合成分的选择性阻滞剂，对所检查的任何中脑区域的结合密度影响最小。目前的结果表明，大鼠腹侧被盖区特定的高亲和力神经降压素结合位点与多巴胺胞体和树突之间存在广泛重叠，从而为在中脑边缘和黑质纹状体投射系统中观察到的神经降压素 - 多巴胺相互作用提供了直接的解剖学基础。
