Rivera Alicia, Cuéllar Beatriz, Girón Francisco J, Grandy David K, de la Calle Adelaida, Moratalla Rosario
Instituto Cajal, Consejo Superior de Investigaciones Cientificas, CSIC, Madrid, Spain.
J Neurochem. 2002 Jan;80(2):219-29. doi: 10.1046/j.0022-3042.2001.00702.x.
Two important aspects of striatal function, exploratory behaviour and motor co-ordination, require the integrity of the dopamine D4 receptor subtype. These receptors are also implicated in the pathophysiology of certain neuropsychiatric disorders. However, the distribution of D4 receptors in the striatum has not yet been described and this situation impairs our understanding of the anatomical substrate in which D4 receptors function. We developed a D4 receptor-specific antibody that has permitted us to investigate the regional and cellular localization of the receptor in the neostriatum of the rat, mouse, cat and monkey. The subcellular distribution and the synaptic organization of this receptor were also determined in the rat striatum. We found moderate levels of D4 receptor expression in the caudoputamen and lower levels in the nucleus accumbens. These receptors were expressed in cell bodies and in the neuropil and were heterogeneously distributed among different striatal compartments, being more abundant in striosomes than in the matrix. At the subcellular level, the receptor immunoreactivity was mainly localized to dendritic shafts and spines. The prominent immunoreactivity observed in the striosomes indicates that integrative processes involved in D4-mediated limbic behaviours occurs through the striosomes rather than accumbens, whereas the motor behaviour is based in the striatal matrix.
纹状体功能的两个重要方面，即探索行为和运动协调，需要多巴胺D4受体亚型的完整性。这些受体也与某些神经精神疾病的病理生理学有关。然而，D4受体在纹状体中的分布尚未被描述，这种情况妨碍了我们对D4受体发挥功能的解剖学基础的理解。我们开发了一种D4受体特异性抗体，它使我们能够研究该受体在大鼠、小鼠、猫和猴新纹状体中的区域和细胞定位。还在大鼠纹状体中确定了该受体的亚细胞分布和突触组织。我们发现尾壳核中D4受体表达水平中等，伏隔核中表达水平较低。这些受体在细胞体和神经纤维网中表达，并且在不同的纹状体区室中分布不均，在纹状小体中比在基质中更丰富。在亚细胞水平上，受体免疫反应主要定位于树突干和树突棘。在纹状小体中观察到的显著免疫反应表明，D4介导的边缘行为所涉及的整合过程是通过纹状小体而非伏隔核发生的，而运动行为则基于纹状体基质。
