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首页> 外文期刊>Life sciences >Neuroadaptations to hyperdopaminergia in dopamine D3 receptor-deficient mice.
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Neuroadaptations to hyperdopaminergia in dopamine D3 receptor-deficient mice.

机译：在多巴胺D3受体缺陷型小鼠中对高多巴胺痛的神经适应。

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The dopamine D3 receptor (D3R) has been implicated in schizophrenia, drug addiction, depression and Parkinson's disease. The D3R is localized post-synaptically on nucleus accumbens neurons, but is also an autoreceptor on dopaminergic neurons in the mesencephalon. Its functional role as autoreceptor is highly debated, but supported by the elevated basal extracellular dopamine levels found in D3R-deficient mice. To investigate the functional role of the D3R in vivo, we used mice with a targeted disruption of the D3R gene. We found a higher basal level of grooming in D3R-deficient mice, compared to their wild-type littermates. This behavior, which is under the control of D1R stimulation, may be related to an increased dopaminergic tone, since no changes in the gene expression of dopamine D1 and D2 receptors were noticed in the striatum of these mice. D3R-deficient mice displayed other neuroadaptive changes, including decreased tyrosine hydroxylase, increased dopamine transporter mRNAs and increased dopamine reuptake in striatum. The level of tyrosine hydroxylase protein was unchanged in the striatum, as preprodynorphin and preproenkephalin gene expressions. All the changes identified in D3R-deficient mice cannot explain hyperdopaminergia, but, on the contrary, tend to attenuate this phenotype. These results support a distinct role for D2R and D3R as autoreceptors: the D2R is the release-regulating and firing rate-regulating autoreceptor, whereas the D3R may control basal dopamine levels in the striatum, by an unknown mechanism, which does not involve regulation of dopamine transporters or tyrosine hydroxylase. This hyperdopaminergia phenotype of D3R-deficient mice may explain their hyperactivity to drug-paired environmental cues.
机译：多巴胺D3受体（D3R）与精神分裂症，药物成瘾，抑郁症和帕金森氏病有关。 D3R突触后定位在伏隔核神经元上，但它也是中脑多巴胺能神经元的自体受体。它作为自体受体的功能作用受到了高度争议，但得到了D3R缺陷型小鼠体内基础细胞外多巴胺水平升高的支持。为了研究D3R在体内的功能作用，我们使用了具有针对性破坏D3R基因的小鼠。与野生型同窝仔相比，我们发现D3R缺陷型小鼠的基础修饰水平更高。这种行为受到D1R刺激的控制，可能与多巴胺能音调升高有关，因为在这些小鼠的纹状体中未发现多巴胺D1和D2受体的基因表达发生变化。 D3R缺陷小鼠表现出其他神经适应性变化，包括酪氨酸羟化酶降低，多巴胺转运蛋白mRNA增加和纹状体中多巴胺再摄取增加。纹状体中酪氨酸羟化酶蛋白的水平没有变化，与前强啡肽和前脑啡肽基因的表达相同。在D3R缺陷型小鼠中鉴定出的所有变化都不能解释高多巴胺痛，但相反，倾向于减弱该表型。这些结果支持D2R和D3R作为自体受体的独特作用：D2R是释放调节和发射速率调节的自体受体，而D3R可能通过未知机制控制纹状体中的基础多巴胺水平，该机制不涉及调节多巴胺转运蛋白或酪氨酸羟化酶。 D3R缺陷小鼠的这种高多巴胺能表型可能解释了它们对药物配对环境线索的过度活跃。

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