A DETAILED MAPPING OF DOPAMINE D-2 RECEPTORS IN RAT CENTRAL-NERVOUS-SYSTEM BY AUTORADIOGRAPHY WITH [I-125] IODOSULPRIDE
A DETAILED MAPPING OF DOPAMINE D-2 RECEPTORS IN RAT CENTRAL-NERVOUS-SYSTEM BY AUTORADIOGRAPHY WITH [I-125] IODOSULPRIDE
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DOI：
10.1016/0306-4522(87)90008-x
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发表时间：
1987-01-01
期刊：
影响因子：
3.3
通讯作者：
SCHWARTZ, JC
中科院分区：
文献类型：
--
作者：
BOUTHENET, ML;MARTRES, MP;SCHWARTZ, JC
用[125]碘代硫代苯甲酰胺衍生物在大鼠脑和脊髓切片上生成光镜放射自显影。在低背景下被[125I]碘标记的部位对应于多巴胺D-2受体，这是通过对在五种多巴胺竞争试剂存在下产生的放射自显影的11个典型区域进行密度分析而建立的药理所显示的。建立D-2受体图谱，包括1个水平、6个矢状面和30个额面，后者以0.5-1 mm的间隔连续制作。标记的区域通过与相应的经典染色切片进行比较来识别。然后，将它们的密度(根据任意等级评级)与以前报道的多巴胺神经支配的密度进行比较，通过多巴胺组织荧光或酪氨酸羟基酶免疫反应的分布图进行评估，发现了三种情况。在纹状体、脑皮质、间脑脊髓和小球周围系统的起源细胞和已建立的投射野对应的区域，D-2受体的密度与多巴胺神经支配的密度大致平行。内侧前脑束注射神经毒素6-羟基多巴胺后，黑质(致密部或网状部)和腹侧被盖区的D-2受体明显减少，提示它们主要分布在多巴胺神经元的树突和核周。大多数其他被描述的多巴胺细胞群区也含有D-2受体。相比之下，许多没有多巴胺神经支配的区域含有D-2受体，有时密度很高。这种情况出现在大脑皮层(I-III层和V-VI层)、小脑(分子层和9小叶内的致密斑块)、海马结构(腔隙分子层)、几个隔核、丘脑和下丘脑的几个核、大的顶盖区域、大量的脑干区(包括脑神经核)等。这种情况可能与仍未检测到的少量多巴胺神经支配的区域相对应，或与D-2受体位于细胞(或细胞部分)上而不接受多巴胺输入有关。最后，几个成熟的多巴胺能区没有显示任何D-2受体标记。尤其是在下丘脑(结节-垂体区和下丘脑区-下丘脑多巴胺系统的起始区或终止区)，而且在海马结构(肺泡、海马伞、门齿状回)、杏仁复合体(前核、基底外侧核、内侧核)也是如此。这些区域可能对应于多巴胺传递不是由D-2受体介导的区域。
The benzamide derivative [125]iodosulpride was used to generate light microscopic autoradiograms on sections of rat brain and spinal cord. Sites specifically labelled by [125I]iodosulpride over a low background correspond to dopamine D-2 receptors as shown by their pharmacology established by densitometric analysis of 11 typical areas from autoradiograms generated in the presence of five dopamine-competing agents. An atlas of D-2 receptors was established using 1 horizontal, 6 sagittal and 30 frontal sections, the latter serially prepared at 0.5-1 mm intervals. Labelled areas were identified by comparison with corresponding, classically stained sections. When their density, rated according to an arbitrary scale, was then compared to that previously reported for dopamine innervation, evaluated from distributional maps of dopamine histofluorescence or tyrosine hydroxylase immunoreactivity, three situations were found. In areas corresponding to cells of origin and established projection fields of the mesostriatal, mesolimbocortical, diencephalospinal and periglomerular systems the density of D-2 receptors generally paralleled that of dopamine innervation. D-2 receptors in substantia nigra (pars compacta or reticulata) and ventral tegmental area were strongly reduced after injections of the neurotoxin 6-hydroxydopamine into the medial forebrain bundle, suggesting their major localization on dendrites and perikarya of dopamine neurons. Most other described dopamine cell group areas also contained D-2 receptors. In contrast many areas without established dopamine innervation contained D-2 receptors, sometimes in high density. This was the case for large areas of the cerebral cortex (layers I-III and V-VI) outside the established projection fields of the mesocortical system, the cerebellum (molecular layer and dense patches within lobule 9), the hippocampal formation (lacunosum moleculare layer), several septal, thalamic and hypothalamic nuclei, large tectal areas, numerous brainstem areas (including cranial nerve nuclei), etc. This situation might correspond to areas with minor and still undetected dopamine innervation or to a localization of D-2 receptors on cells (or cell parts) not receiving dopamine inputs. Finally several well-established dopaminergic areas did not reveal any D-2 receptor labelling. This was particularly the case in the hypothalamus (areas of origin or termination of the tuberohypophyseal and incertohypothalamic dopamine systems) but also in the hippocampal formation (alveus, fimbria, hilus dentate gyrus), amygdaloid complex (anterior, basolateral, medial nuclei). These areas might correspond to those in which the dopamine transmission is not mediated by D-2 receptors.