Postnatal ontogeny of dopamine D3 receptors in the mouse brain: autoradiographic evidence for a transient cortical expression.

J Demotes-Mainard, C Henry, Y Jeantet, J Arsaut, E Arnauld
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Abstract

The expression of dopamine D3 receptors is relatively low in the adult brain and is mainly restricted to the limbic region. We studied here the postnatal development of these receptors in the mouse brain by quantitative autoradiography using [3H](+/-)-7-OH-DPAT as ligand. In all brain regions examined, there was a progressive increase in D3 receptor protein expression from birth to the weaning period, a pattern reminiscent of that of dopamine D2 rather than D1 receptors. In broad outline, the regional distribution of D3 receptors during brain ontogeny resembled that observed in adult animals, the labelling being detected earlier in the structures with the higher density in the adult. The highest and earliest expression of D3 receptors was observed in the islands of Calleja and olfactory tubercle, where [3H]7-OH-DPAT binding was already present at birth. D3 receptors appeared at postnatal day 4 in the nucleus accumbens, at postnatal day 8 in the substantia nigra, in the medial mamillary nucleus and in the anterior thalamic complex, and at postnatal day 11 in the archaeocerebellum. In contrast to other brain structures where the developmental pattern of D3 receptor expression parallelled its distribution and density in the adult brain, there was a transient cortical expression of [3H]7-OH-DPAT binding between postnatal days 6 and 15, confined to a longitudinal strip in the dorso-lateral part of the parietal cortex. This expression had disappeared by postnatal day 21 and was not detected in adult mice. These developmental findings, and particularly the transient cortical expression of functional receptors, point to the involvement of D3 receptors in ontogenic processes.

小鼠大脑中多巴胺D3受体的出生后个体发育:短暂皮层表达的放射自显影证据。
多巴胺D3受体在成人大脑中的表达相对较低,主要局限于边缘区。本研究以[3H](+/-)-7- oh - dpat为配体,采用定量放射自显影技术研究了这些受体在小鼠脑内的出生后发育。在所有被检查的大脑区域中,从出生到断奶期间,D3受体蛋白的表达逐渐增加,这种模式让人想起多巴胺D2而不是D1受体。大体上,D3受体在脑个体发育过程中的区域分布与在成年动物中观察到的相似,标记在成年动物中密度较高的结构中被检测到更早。在Calleja岛和嗅结节岛,D3受体的表达最高和最早,在出生时就已经存在[3H]7-OH-DPAT结合。D3受体在出生后第4天出现在伏隔核中,在出生后第8天出现在黑质、内侧乳状核和丘脑前复合体中,在出生后第11天出现在原始小脑中。与D3受体表达的发育模式与其在成人大脑中的分布和密度平行的其他大脑结构相反,在出生后第6天至第15天之间,[3H]7-OH-DPAT结合在皮层中有短暂的表达,局限于顶叶皮层背外侧的纵向条带。这种表达在出生21天后消失,在成年小鼠中未检测到。这些发育上的发现,特别是皮层功能受体的短暂表达,表明D3受体参与了个体形成过程。
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