Central overexpression of angiotensin AT(1A) receptors prevents dopamine D(2) receptor regulation of alcohol consumption in mice.
Central overexpression of angiotensin AT(1A) receptors prevents dopamine D(2) receptor regulation of alcohol consumption in mice.
复制标题
血管紧张素 AT(1A) 受体的中枢过度表达可阻止多巴胺 D(2) 受体对小鼠饮酒的调节。
DOI：
10.1111/j.1530-0277.2007.00399.x
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Lawrence,AndrewJ
中科院分区：
文献类型：
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作者：
Moore,Rosanna;Krstew,ElenaV;Kirchhoff,Jeppe;Davisson,RobinL;Lawrence,AndrewJ
背景：虽然血管紧张素受体存在于多巴胺能神经元的胞体和终末，但围绕血管紧张素在酒精摄入中的潜在作用仍存在争议。方法：利用脑特异性高表达血管紧张素AT1A受体的转基因小鼠(NSE-AT1Amice)，我们研究了血管紧张素在酒精消耗和酒精诱导的多巴胺能系统调节中的作用。结果：过度表达的AT1A受体在功能上的相关性被证实为24小时脱水后过度水化反应。NSE-AT1Amice显示出对酒精的高度偏好(与野生型小鼠相似)；然而，拉氯普利治疗对NSE-AT1Amice小鼠的酒精消耗量没有影响，而显著减少了野生型小鼠的酒精消耗量。相比之下，与野生型相比，NSE-AT1Amice对拉氯普利的敏感性增强，这是因为腹侧中脑D2受体上调。结论：虽然纹状体神经元上血管紧张素AT1A受体的表达对基础饮酒或喜好没有影响，但AT1A受体确实调节了多巴胺D2受体对酒精调节的敏感性和D2受体拮抗剂减少饮酒的能力。
Background:While angiotensin receptors are found on the soma and terminals of dopaminergic neurons, controversy surrounds the potential role of angiotensin in alcohol consumption.Methods:Using a transgenic mouse with a brain‐specific overexpression of angiotensin AT1Areceptors (NSE‐AT1Amice), we have examined the role of angiotensin in alcohol consumption and alcohol‐induced regulation of the dopaminergic system.Results:The functional relevance of the overexpressed AT1Areceptors was confirmed by an exaggerated rehydration response following 24‐hour dehydration. NSE‐AT1Amice showed a high preference for alcohol (similar to wild‐type mice); yet, raclopride treatment had no effect on alcohol consumption in NSE‐AT1Amice, while significantly reducing consumption in wild‐type mice. In contrast, NSE‐AT1Amice showed enhanced sensitivity to raclopride compared with wild types in terms of D2receptor up‐regulation within the ventral mesencephalon. In addition, striatal D2receptors in NSE‐AT1Amice were sensitive to up‐regulation by chronic alcohol consumption.Conclusions:Collectively, these data imply that while expression of angiotensin AT1Areceptors on striatal neurons has no impact upon basal alcohol consumption or preference, AT1Areceptors do modulate the sensitivity of dopamine D2receptors to regulation by alcohol and the ability of a D2receptor antagonist to reduce consumption.