Pickel V M, Chan J, Sesack S R
Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021.
Brain Res. 1993 Feb 5;602(2):275-89. doi: 10.1016/0006-8993(93)90693-h.
Dynorphin and other kappa opioid agonists are thought to elicit aversive actions and changes in motor activity through direct or indirect modulation of dopamine neurons in ventral tegmental area (VTA) and substantia nigra (SN), respectively. We comparatively examined the immunoperoxidase localization of anti-dynorphin A antiserum in sections through the VTA and SN of adult rat brain to assess whether there were common or differential distributions of this opioid peptide relative to the dopamine neurons. We also more directly examined the relationship between dynorphin terminals and dopamine neurons in VTA and SN by combining immunoperoxidase labeling of rabbit dynorphin antiserum and immunogold-silver detection of mouse antibodies against tyrosine hydroxylase (TH) in single sections through the VTA and SN. Light microscopy showed dynorphin-like immunoreactivity (DY-LI) in varicose processes. These were relatively sparse in VTA and were unevenly distributed in the SN, with little labeling in the pars compacta (pcSN) and the highest density of DY-LI in the medial and lateral pars reticulata (prSN). Electron microscopy established that the regional differences were attributed to differences in density (number/unit area) of immunoreactive profiles. The profiles containing DY-LI were designated as axon terminals based on having diameters greater than 0.1 micron, few microtubules and many synaptic vesicles. In both the VTA and SN, the dynorphin-labeled terminals contained primarily small (35-40 nm) clear vesicles. These vesicles were rimmed with peroxidase immunoreactivity and were often seen clustered above axodendritic synapses. These synaptic specializations were usually symmetric; however a few asymmetric densities also were formed by immunoreactive terminals in both VTA and SN. Additionally, most of the dynorphin-labeled terminals contained 1-2, but occasionally 7 or more intensely peroxidase positive dense core vesicles (DCVs). Approximately 60% of the DCVs were located near axolemmal surfaces. The axolemmal surfaces contacted by immunoreactive DCVs were more often apposed to dendrites in the VTA; while in the SN other axon terminals were the most commonly apposed neuronal profiles. In both regions, a substantial proportion of the plasmalemmal surface in contact with the labeled DCVs was apposed to astrocytic processes.(ABSTRACT TRUNCATED AT 400 WORDS)
强啡肽及其他κ阿片受体激动剂被认为分别通过直接或间接调节腹侧被盖区（VTA）和黑质（SN）中的多巴胺能神经元，引发厌恶行为及运动活动的改变。我们比较研究了抗强啡肽A抗血清在成年大鼠脑VTA和SN切片中的免疫过氧化物酶定位，以评估该阿片肽相对于多巴胺能神经元是否存在共同或差异分布。我们还通过在VTA和SN的单切片中联合兔强啡肽抗血清的免疫过氧化物酶标记和抗酪氨酸羟化酶（TH）小鼠抗体的免疫金银检测，更直接地研究了VTA和SN中强啡肽终末与多巴胺能神经元之间的关系。光学显微镜显示曲张突起中有强啡肽样免疫反应性（DY-LI）。这些在VTA中相对稀疏，在SN中分布不均，致密部（pcSN）标记很少，而在内侧和外侧网状部（prSN）中DY-LI密度最高。电子显微镜证实区域差异归因于免疫反应性轮廓密度（数量/单位面积）的差异。基于直径大于0.1微米、微管少且突触小泡多，含有DY-LI的轮廓被指定为轴突终末。在VTA和SN中，强啡肽标记的终末主要含有小（35 - 40纳米）清亮小泡。这些小泡边缘有过氧化物酶免疫反应性，且常聚集成簇位于轴突-树突突触上方。这些突触特化通常是对称的；然而在VTA和SN中，免疫反应性终末也形成了一些不对称致密结构。此外，大多数强啡肽标记的终末含有1 - 2个，但偶尔有7个或更多强烈过氧化物酶阳性的致密核心小泡（DCV）。约60%的DCV位于轴膜表面附近。免疫反应性DCV接触的轴膜表面在VTA中更常与树突相邻；而在SN中，其他轴突终末是最常相邻的神经元轮廓。在两个区域中，与标记DCV接触的大部分质膜表面与星形胶质细胞突起相邻。（摘要截断于400字）
