Delta opioid receptors in brain function and diseases.
Delta opioid receptors in brain function and diseases.
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DOI：
10.1016/j.pharmthera.2013.06.003
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发表时间：
2013-10
影响因子：
13.5
通讯作者：
Kieffer, Brigitte L.
中科院分区：
文献类型：
--
作者：
Chung, Paul Chu Sin;Kieffer, Brigitte L.
近年来，δ阿片受体（DOR）是治疗脑疾病的有吸引力的靶点的证据得到了加强。这种受体在脑中广泛表达，结合内源性阿片肽，并显示出与μ和κ阿片受体高度不同的功能特征。我们对DOR功能的了解已经从使用药理学工具和遗传方法的体内研究中取得了巨大进展。这种受体在减少慢性疼痛中的重要作用已被广泛综述，因此，本次审查的重点是精神和其他神经系统疾病相关的δ受体活性的方面。DOR激动剂的有益作用现在在情绪反应和情绪障碍的背景下得到了很好的确立。DOR激活还调节药物奖赏、抑制控制和学习过程，但δ化合物是否可能代表治疗药物滥用的有用药物仍然是开放的。δ激动剂的致癫痫和运动刺激作用似乎具有药物依赖性，这些作用在DOR时的偏倚激动可能性值得进一步研究，以增加δ治疗的获益/风险比。DOR活性的神经保护作用代表了一个即将到来的研究领域。DOR研究的未来发展将受益于在细胞和电路水平上对DOR功能的深入研究。
Evidence that the delta opioid receptor (DOR) is an attractive target for the treatment of brain disorders has strengthened in recent years. This receptor is broadly expressed in the brain, binds endogenous opioid peptides, and shows as functional profile highly distinct from those of mu and kappa opioid receptors. Our knowledge of DOR function has enormously progressed from in vivo studies using pharmacological tools and genetic approaches. The important role of this receptor in reducing chronic pain has been extensively overviewed; therefore this review focuses on facets of delta receptor activity relevant to psychiatric and other neurological disorders. Beneficial effects of DOR agonists are now well established in the context of emotional responses and mood disorders. DOR activation also regulates drug reward, inhibitory controls and learning processes, but whether delta compounds may represent useful drugs in the treatment of drug abuse remains open. Epileptogenic and locomotor-stimulating effects of delta agonists appear drug-dependent, and the possibility of biased agonism at DOR for these effects is worthwhile further investigations to increase benefit/risk ratio of delta therapies. Neuroprotective effects of DOR activity represent a forthcoming research area. Future developments in DOR research will benefit from in-depth investigations of DOR function at cellular and circuit levels.
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