Localization of dopamine D3 receptors to mesolimbic and D2 receptors to mesostriatal regions of human forebrain.

We characterized the binding of [125I]epidepride to dopamine D2-like and D3-like receptors in tissue sections of human striatum. The competition for binding of [125I]epidepride by domperidone, quinpirole, and 7-hydroxy-N,N-di(1-propyl)-2-aminotetralin (7-OH-DPAT) was best fit by assuming one site in the caudate but two sites in nucleus accumbens. Guanosine 5'-[beta, gamma-imido]triphosphate showed a large modulatory influence in agonist inhibition of [125I]epidepride binding in caudate but not in nucleus accumbens. The binding of [125I]epidepride in the presence of 7-OH-DPAT (1000-fold selective for D3-like versus D2-like sites) and domperidone (20-fold selective for D2-like versus D3-like sites) was used to quantify the numbers of D2-like and D3-like receptors in areas of human brain. The distribution of D2-like and D3-like receptors was largely nonoverlapping. Binding of [125I]epidepride to D3-like receptors was negligible in the dorsal striatum but was concentrated in islands of dense binding in the nucleus accumbens and ventral putamen that aligned with acetylcholinesterase-poor striosomes. Binding to D3-like receptors was also enriched in the internal globus pallidus, ventral pallidum, septum, islands of Calleja, nucleus basalis, amygdalostriatal transition nucleus of the amygdala, central nucleus of the amygdala, and ventral tegmental area. Binding of [125I]epidepride to D2 but not D3 receptors was detected in cortex and hippocampus. IMAGES:

本研究对[125I]依匹必利（[125I]epidepride）在人类纹状体组织切片中与多巴胺D2样受体（dopamine D2-like receptors）及D3样受体（dopamine D3-like receptors）的结合特性进行了表征。多潘立酮（domperidone）、喹吡罗（quinpirole）以及7-羟基-N,N-二(1-丙基)-2-氨基四氢萘（7-hydroxy-N,N-di(1-propyl)-2-aminotetralin, 7-OH-DPAT）对[125I]依匹必利结合的竞争结合实验结果经拟合后显示：尾状核（caudate）仅存在单一结合位点，而伏隔核（nucleus accumbens）则存在两个结合位点。鸟苷5'-[β,γ-亚氨基]三磷酸（Guanosine 5'-[beta, gamma-imido]triphosphate）可对尾状核中激动剂介导的[125I]依匹必利结合抑制产生显著调控作用，但对伏隔核无此效果。借助对D3样受体具有1000倍选择性的7-OH-DPAT，以及对D2样受体具有20倍选择性的多潘立酮共同存在下的[125I]依匹必利结合实验，我们实现了人类脑内不同区域D2样与D3样受体数量的定量分析。D2样与D3样受体的分布区域整体上不存在重叠。[125I]依匹必利与D3样受体的结合在背侧纹状体（dorsal striatum）中几乎可忽略不计，但在伏隔核与腹侧壳核（ventral putamen）中则富集于与乙酰胆碱酯酶贫化纹状体小体（acetylcholinesterase-poor striosomes）对齐的高密度结合岛中。D3样受体的结合信号还在内侧苍白球（internal globus pallidus）、腹侧苍白球（ventral pallidum）、隔区（septum）、Calleja岛（islands of Calleja）、基底核（nucleus basalis）、杏仁体的杏仁纹状体过渡核（amygdalostriatal transition nucleus of the amygdala）、杏仁中央核（central nucleus of the amygdala）以及腹侧被盖区（ventral tegmental area）中富集。在大脑皮层（cortex）与海马体（hippocampus）中仅检测到[125I]依匹必利与D2受体的结合，未发现其与D3受体的结合。图像数据：