Dopamine transporter development in postnatal rat striatum, an autoradiographic study with [3H]WIN 35,428
Dopamine transporter development in postnatal rat striatum, an autoradiographic study with [3H]WIN 35,428
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DOI：
10.1016/s0165-3806(97)00135-1
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发表时间：
1997-12-19
期刊：
影响因子：
--
通讯作者：
Murrin, LC
中科院分区：
文献类型：
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作者：
Coulter, CL;Happe, HK;Murrin, LC
多巴胺转运蛋白介导可卡因的强化作用，因此在人类可卡因成瘾中发挥核心作用，并可能提供诱导产前可卡因暴露效应的机制。这种可能性刺激了对这种转运蛋白的正常和异常发育的兴趣。[H-3]WIN 35，428是一种可卡因类似物，可用于研究纹状体和其他大脑区域中多巴胺转运蛋白的分布和密度。用[H-3]WIN 35，428定量放射自显影法测定大鼠纹状体多巴胺转运体的出生后发育。多巴胺转运蛋白水平在出生时较低，到第15天增加，随后在出生后发育后期增长更快。大多数转运位点出现在第15天之后。从外侧到内侧和从前部到后部的转运体密度梯度在发育早期就已建立，而且在第15天时，纹状体中的转运体也有一个早期浓度，很难确定。这里描述的发育模式和使用其他多巴胺转运蛋白配体的研究之间的差异表明，这些药物的转运蛋白结合位点存在显着差异。转运蛋白配体结合特征的这些差异可能反映了转运蛋白翻译后修饰的发育变化和/或功能活性的变化，而不仅仅是转运蛋白的存在。(C)1997年Elsevier Science B.V.
The dopamine transporter mediates the reinforcing effects of cocaine, thus playing a central role in human cocaine addiction, and perhaps providing the mechanism for inducing the effects of prenatal cocaine exposure. This possibility has stimulated growing interest in the normal and abnormal development of this transporter. [H-3]WIN 35,428 is a cocaine analog that is useful for studying the distribution and density of the dopamine transporter in striatum and other brain regions. The postnatal development of the dopamine transporter in the rat striatum was measured by quantitative autoradiography with [H-3]WIN 35,428. Dopamine transporter levels were low at birth, increased through day 15, followed by much more rapid growth in late postnatal development. The majority of the transporter sites appeared after day 15. Lateral to medial and anterior to posterior gradients in transporter density were established early during development, and there was also an early concentration of transporter in striosomes that became difficult to identify by day 15. Differences between the developmental patterns described here and studies using other ligands for the dopamine transporter suggest there are significant differences in the transporter binding sites for these drugs. These differences in transporter ligand binding characteristics may reflect developmental changes in post-translational modification of the transporter and/or changes in the functional activity rather than simply the presence of the transporter. (C) 1997 Elsevier Science B.V.