Taylor George T, Manzella Francesca
Behavioral Neuroscience/ Psychology Univ. Missouri - St. Louis, One University Blvd, St. Louis, MO 63121 USA.
Curr Neuropharmacol. 2016;14(2):165-76. doi: 10.2174/1570159x13666150727220944.
Opioids are traditionally associated with pain, analgesia and drug abuse. It is now clear, however, that the opioids are central players in mood. The implications for mood disorders, particularly clinical depression, suggest a paradigm shift from the monoamine neurotransmitters to the opioids either alone or in interaction with monoamine neurons. We have a special interest in dynorphin, the last of the major endogenous opioids to be isolated and identified. Dynorphin is derived from the Greek word for power, dynamis, which hints at the expectation that the neuropeptide held for its discoverers. Yet, dynorphin and its opioid receptor subtype, kappa, has always taken a backseat to the endogenous b-endorphin and the exogenous morphine that both bind the mu opioid receptor subtype. That may be changing as the dynorphin/ kappa system has been shown to have different, often opposite, neurophysiological and behavioral influences. This includes major depressive disorder (MDD). Here, we have undertaken a review of dynorphin/ kappa neurobiology as related to behaviors, especially MDD. Highlights include the unique features of dynorphin and kappa receptors and the special relation of a plant-based agonist of the kappa receptor salvinorin A. In addition to acting as a kappa opioid agonist, we conclude that salvinorin A has a complex pharmacologic profile, with potential additional mechanisms of action. Its unique neurophysiological effects make Salvinorina A an ideal candidate for MDD treatment research.
传统上，阿片类药物与疼痛、镇痛和药物滥用相关。然而，现在很清楚的是，阿片类药物在情绪调节中起着核心作用。这对情绪障碍，尤其是临床抑郁症的启示是，可能需要从单胺神经递质转向单独的阿片类药物，或者转向与单胺神经元相互作用的阿片类药物，这意味着一种范式转变。我们对强啡肽特别感兴趣，它是最后一种被分离和鉴定的主要内源性阿片类药物。强啡肽这个词来源于希腊语中的“力量”一词，即“dynamis”，这暗示了这种神经肽给其发现者带来的期望。然而，强啡肽及其阿片受体亚型κ，在内源性β-内啡肽和外源性吗啡面前一直处于次要地位，后两者都与μ阿片受体亚型结合。随着强啡肽/κ系统已被证明具有不同的、通常是相反的神经生理和行为影响，这种情况可能正在发生变化。这其中包括重度抑郁症（MDD）。在此，我们对与行为，尤其是与重度抑郁症相关的强啡肽/κ神经生物学进行了综述。重点包括强啡肽和κ受体的独特特征，以及κ受体植物性激动剂沙维诺林A的特殊关系。除了作为κ阿片激动剂外，我们得出结论，沙维诺林A具有复杂的药理学特征，可能还有其他潜在的作用机制。其独特的神经生理效应使沙维诺林A成为重度抑郁症治疗研究的理想候选药物。
