7-OH-DPAT and PD 128907 selectively activate the D3 dopamine receptor in a novel environment
7-OH-DPAT and PD 128907 selectively activate the D3 dopamine receptor in a novel environment
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DOI：
10.1038/sj.npp.1300018
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发表时间：
2003-01-01
影响因子：
7.6
通讯作者：
Richtand, NM
中科院分区：
文献类型：
--
作者：
Pritchard, LM;Logue, AD;Richtand, NM
D3 多巴胺受体主要在大脑边缘区域表达，似乎在啮齿类动物的运动行为中发挥抑制作用。有证据表明 D3 受体在神经精神疾病的病理学中具有潜在作用。然而，由于缺乏特征明确的选择性配体以及有关 D3 受体敲除小鼠行为表型的相互矛盾的信息，阐明 D3 受体功能的进展受到阻碍。在这里，我们描述了评估 (+/-)-7-羟基-N,N-二正丙基-2-氨基四氢萘 (7-OH-DPAT) 和 PD 128907 的行为影响的研究，这两种 D3 受体激动剂的体内选择性一直是一个颇具争议的话题。我们证明，这两种化合物都能抑制野生型 (WT) 小鼠在新环境条件下的运动，但在 D3 受体敲除小鼠中在相同条件下没有可测量的行为效应。此外，我们证明，在低 D3 选择性剂量下，这些化合物对已适应测试环境的 WT 和 D3 受体敲除小鼠均没有行为影响。这些发现表明，D3 受体刺激会抑制新奇刺激的运动，并为在体内使用 7-OH-DPAT 和 PD 128907 作为 D3 受体激动剂奠定了条件。讨论了这些观察结果的潜在影响。
The D3 dopamine receptor is expressed primarily in limbic brain areas, and appears to play an inhibitory role in rodent locomotor behavior. Evidence suggests a potential role for the D3 receptor in the pathology of neuropsychiatric disease. Progress in elucidating D3 receptor function has been hampered, however, by a lack of well-characterized, selective ligands and by conflicting information regarding the behavioral phenotype of D3 receptor knockout mice. Here, we describe studies evaluating the behavioral effects of (+/-)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (7-OH-DPAT) and PD 128907, two D3 receptor agonists whose in vivo selectivity has been a topic of considerable controversy. We demonstrate that both compounds inhibit locomotion under novel environmental conditions in wild-type (WT) mice, but are without measurable behavioral effect under identical conditions in D3 receptor knockout mice. Additionally, we demonstrate that at low, D3 selective doses, these compounds are without behavioral effect in both WT and D3 receptor knockout mice that have acclimated to the testing environment. These findings suggest that D3 receptor stimulation inhibits novelty-stimulated locomotion, and establish conditions for the use of 7-OH-DPAT and PD 128907 as D3 receptor agonists in vivo. Potential implications of these observations are discussed.