Wamsley J K, Gehlert D R, Filloux F M, Dawson T M
Western Institute of Neuropsychiatry, Salt Lake City, UT.
J Chem Neuroanat. 1989 May-Jun;2(3):119-37.
The distribution of dopamine type 1 (D-1) and dopamine type 2 (D-2) receptors in the brain have been compared as assessed by the technique of autoradiography after labelling with highly selective ligands. D-1 receptors, as evidenced by the specific binding of [3H]R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-IH-3-benzazepine -7- ol (SCH 23390), were found in high concentrations in the caudate-putamen, nucleus accumbens, islands of Calleja, olfactory tubercle and the zona reticulata of the substantia nigra. A similar but distinct distribution was seen for [3H]sulpiride, a ligand which is highly selective for D-2 receptors. Like [3H]SCH 23390, this ligand also labelled the caudate-putamen, nucleus accumbens, islands of Calleja and the olfactory tubercle; however, only a very low density of D-2 receptors could be found in the zona reticulata of the substantia nigra, while a greater degree of binding was present in the zona compacta. Additional brain areas which contained D-1 but not D-2 receptors included the cerebral cortex, accessory olfactory nucleus, amygdala, thalamus, suprachiasmatic nucleus, choroid plexus, claustrum, endopiriform nucleus, zona incerta, dorsal lateral geniculate nucleus and the dentate gyrus. D-2 receptors were also found in areas which appeared to contain only low amounts of D-1 receptors such as the glomerular layer of the olfactory bulb, bed nucleus of the stria terminalis, hypothalamus, habenula, stratum lacunosum moleculare of the hippocampus, intermediate lobe of the pituitary, lateral mammillary nucleus, periaqueductal gray, inferior colliculus, nodulus of the cerebellum and the dorsal horn of the spinal cord. The results show the precise localization of dopamine receptors throughout the brain and provide a means of direct comparison between the distribution of dopamine receptor subtypes. These subtypes are pharmacologically and anatomically distinct entities and their comparison indicates areas where additional biochemical and neuroanatomical studies may be performed to elucidate the roles for these receptor subtypes in the central nervous system.
在用高选择性配体标记后,通过放射自显影技术评估了大脑中多巴胺1型(D-1)和多巴胺2型(D-2)受体的分布情况。用[3H]R-(+)-8-氯-2,3,4,5-四氢-3-甲基-5-苯基-1H-3-苯并氮杂卓-7-醇(SCH 23390)的特异性结合所证实,D-1受体在尾状核-壳核、伏隔核、Calleja岛、嗅结节和黑质网状带中浓度较高。对于[3H]舒必利(一种对D-2受体具有高度选择性的配体),观察到了类似但不同的分布。与[3H]SCH 23390一样,这种配体也标记了尾状核-壳核、伏隔核、Calleja岛和嗅结节;然而,在黑质网状带中仅发现极低密度的D-2受体,而在黑质致密带中存在更高程度的结合。其他含有D-1但不含D-2受体的脑区包括大脑皮层、副嗅核、杏仁核、丘脑、视交叉上核、脉络丛、屏状核、内梨状核、未定带、背外侧膝状体核和齿状回。在似乎仅含有少量D-1受体的区域也发现了D-2受体,如嗅球的肾小球层、终纹床核、下丘脑、缰核、海马分子层的腔隙层、垂体中间叶、外侧乳头核、导水管周围灰质、下丘、小脑小结和脊髓背角区。结果显示了多巴胺受体在整个大脑中的精确定位,并提供了一种直接比较多巴胺受体亚型分布的方法。这些亚型在药理学和解剖学上是不同的实体,它们的比较表明了可能需要进行额外的生化和神经解剖学研究以阐明这些受体亚型在中枢神经系统中作用的区域。