Quantitative autoradiographic mapping of rat brain dopamine D3 binding with [(125)I]7-OH-PIPAT: evidence for the presence of D3 receptors on dopaminergic and nondopaminergic cell bodies and terminals.
Quantitative autoradiographic mapping of rat brain dopamine D3 binding with [(125)I]7-OH-PIPAT: evidence for the presence of D3 receptors on dopaminergic and nondopaminergic cell bodies and terminals.
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发表时间：
2000-12
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通讯作者：
Gregg D. Stanwood;Roman Artymyshyn;M. Kung;H. Kung;I. Lucki;P. Mcgonigle
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作者：
Gregg D. Stanwood;Roman Artymyshyn;M. Kung;H. Kung;I. Lucki;P. Mcgonigle
采用定量放射自显影技术研究了多巴胺D3受体在大鼠脑内的区域分布和细胞定位。[(125)I]7-OH-PIPAT以饱和和可逆的方式结合，并对单个gtp不敏感位点表现出亚纳摩尔的亲和力。克隆D3受体的药理学特征和非特异性结合一致低。在胼胝体岛、伏隔核、腹侧苍白球、黑质和小脑第9小叶和第10小叶中检测到最高水平的D3受体。这种配体的高比活性也允许在其他区域检测D3受体，包括5 -羟色胺能背核和中缝核中，表明这种受体的分布比以前所认识的更广泛。分别注射神经毒素检测D3受体在含多巴胺能细胞和终末区域的细胞定位。多巴胺能神经元损伤后，伏隔核和黑质中[(125)I]7-OH-PIPAT结合减少50%。喹啉酸损伤源自伏隔核的神经元也会导致伏隔核、黑质和腹侧白质中D3受体减少约50%。5,7 -二羟色胺损伤的5 -羟色胺能细胞和过程未产生7-OH-PIPAT结合的变化[(125)I]。这些结果表明D3受体存在于几个以前未发现的大脑区域，并表明D3受体在中脑边缘多巴胺系统中多巴胺能和非多巴胺能细胞的体树突和终末水平表达。
The regional distribution and cellular localization of dopamine D3 receptors in the rat brain was examined using quantitative autoradiography. [(125)I]7-OH-PIPAT bound in a saturable and reversible manner and exhibited subnanomolar affinity for a single population of GTP-insensitive sites. The pharmacological profile was characteristic of cloned D3 receptors and nonspecific binding was uniformly low. The highest levels of D3 receptors were measured in the islands of Calleja, nucleus accumbens, ventral pallidum, substantia nigra, and lobules 9 and 10 of the cerebellum. The high specific activity of this ligand also allowed detection of D3 receptors in other regions, including the serotonergic dorsal and median raphe nuclei, indicating that the distribution of this receptor is more widespread than previously appreciated. The cellular localization of D3 receptors in regions containing dopaminergic cells and terminals was examined by discrete injection of neurotoxins. Lesion of dopaminergic neurons with 6-hydroxydopamine produced 50% decreases in [(125)I]7-OH-PIPAT binding in the nucleus accumbens and substantia nigra. Quinolinic acid lesion of neurons originating in the nucleus accumbens also produced approximately 50% decreases in D3 receptors in the nucleus accumbens, substantia nigra, and ventral pallidum. 5, 7-Dihydroxytryptamine lesion of serotonergic cells and processes produced no changes in [(125)I]7-OH-PIPAT binding. These results demonstrate the presence of D3 receptors in several brain regions not previously identified and suggest that D3 receptors are expressed at somatodendritic and terminal levels of both dopaminergic and nondo-paminergic cells within the mesolimbic dopamine system.