Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR7104 CNRS/Université de Strasbourg, U964 INSERM, Illkirch, France.
Pharmacol Ther. 2013 Oct;140(1):112-20. doi: 10.1016/j.pharmthera.2013.06.003. Epub 2013 Jun 10.
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.
近年来，δ 阿片受体（DOR）作为治疗脑疾病的有吸引力的靶点的证据不断增强。该受体在大脑中广泛表达，与内源性阿片肽结合，并表现出与 μ 和 κ 阿片受体截然不同的功能特征。我们对 DOR 功能的了解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。该受体在减轻慢性疼痛方面的重要作用已被广泛综述；因此，本综述重点介绍与精神和其他神经疾病相关的 δ 受体活性方面。DOR 激动剂在情绪反应和情绪障碍方面的有益作用已得到充分证实。DOR 激活还调节药物奖赏、抑制控制和学习过程，但 δ 化合物是否可能成为治疗药物滥用的有用药物仍存在争议。δ 激动剂的致痫和运动刺激作用似乎与药物有关，对于这些作用，DOR 的偏性激动作用值得进一步研究，以提高 δ 治疗的获益/风险比。DOR 活性的神经保护作用是一个即将到来的研究领域。DOR 研究的未来发展将受益于对 DOR 在细胞和回路水平上的功能的深入研究。
