Ultrastructural localization of the serotonin 2A receptor in dopaminergic neurons in the ventral tegmental area
Ultrastructural localization of the serotonin 2A receptor in dopaminergic neurons in the ventral tegmental area
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DOI：
10.1016/s0006-8993(00)02062-x
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发表时间：
2000-05-12
期刊：
影响因子：
2.9
通讯作者：
Pickel, VM
中科院分区：
文献类型：
--
作者：
Doherty, MD;Pickel, VM
5-羟色胺（5-羟色胺，5-HT）2A受体拮抗剂是临床上有效的抗精神病药，可以差异化地靶向分布在臂旁（PB）和旁黑质（PN）腹侧被盖区（VTA）的中皮质和中边缘多巴胺能神经元。我们检查了大鼠 VTA 这些分区中 5-HT2A 受体的超微结构免疫细胞化学定位，以确定 (1) 受体激活的功能位点，以及 (2) 受体与通过酪氨酸羟化酶 (TH) 含量鉴定的多巴胺能神经元之间的细胞关联。含有 5-HT2A 受体标记的神经元分布的平均面积密度在 PB 和 PN VTA 中没有显着差异。在每个区域中，大约 44% 的 5-HT2A 标记轮廓是树突，而其余的主要是轴突。树突状 5-HT2A 免疫反应性通常位于类似于光滑内质网的膜细胞质细胞器，并且更罕见地位于未标记的轴突末端接触下方的质膜片段。在一些轴突初始片段和许多小的无髓鞘轴突的细胞质内也发现了 5-HT2A 标记。 PB 或 PN VTA 中大约 40% 的 5-HT2A 标记树突状图含有 TH。我们的结果表明，VTA 中的 5-HT2A 受体主要是细胞质的，并且在调节 PB 和 PN VTA 中的多巴胺能神经元中发挥同样重要的作用。这些结果还表明 5-HT2A 受体参与非多巴胺能神经元的突触后激活，并且可能涉及源自或穿过这些区域的轴突末端的突触前释放。 (C) 2000 Elsevier Science B.V. 保留所有权利。
Serotonin (5-hydroxytryptamine, 5-HT) 2A receptor antagonists are clinically effective antipsychotics that may differentially target mesocortical and mesolimbic dopaminergic neurons having partially segregated distribution in the parabrachial (PB) and paranigral (PN) ventral tegmental area (VTA). We examined the ultrastructural immunocytochemical localization of the 5-HT2A receptor in these subdivisions of rat VTA, to determine (1) the functional sites for receptor activation, and (2) cellular associations between the receptor and dopaminergic neurons identified by their content of tyrosine hydroxylase (TH). The mean area density of neuronal profiles containing 5-HT2A receptor labeling was not significantly different in the PB and PN VTA. In each region approximately 44% of the 5-HT2A labeled profiles were dendrites while the remainder were mainly axons. Dendritic 5-HT2A-immunoreactivity was often localized to membranous cytoplasmic organelles resembling smooth endoplasmic reticulum, and to more rarely to segments of the plasma membrane beneath contacts from unlabeled axon terminals. 5-HT2A labeling was also seen within the cytoplasm of a few axon initial segments and many small unmyelinated axons. Approximately 40% of the 5-HT2A-labeled dendritic profiles contained TH in either PB or PN VTA. Our results suggest that 5-HT2A receptors in VTA are largely cytoplasmic and play an equally important role in modulating dopaminergic neurons in PB and PN VTA. These results also implicate 5-HT2A receptors in the postsynaptic activation of non-dopaminergic neurons and possibly the presynaptic release from terminals of axons originating in, or passing through, these regions. (C) 2000 Elsevier Science B.V. All rights reserved.