Cohen M R, Pickar D
J Clin Psychopharmacol. 1981 Jul;1(4):223-31. doi: 10.1097/00004714-198107000-00007.
The discovery of an endogenous opioid system has been rapidly followed by animal studies suggesting its importance in neuroendocrine regulation and behavior. Abnormalities of these functions in affective illness suggest that evaluation of behavioral and hormonal responses following the clinical administration of opiate agonists or antagonists might yield information pertinent to the pathogenesis, diagnosis, and treatment of depression. However, initial double-blind controlled clinical studies have yielded little evidence to support this suggested involvement of the opioid system in affective illness. Acute administration of opiate agonists has sometimes yielded a mild antidepressant response in depression, and naloxone has occasionally been reported beneficial in mania. There is, however, little to suggest that these responses are specific to affective illness. A decreased prolactin response to morphine administration has been reported in depression, but is not direct evidence of opioid system dysfunction in depression since abnormal prolactin responses to other challenges in depression have previously been reported. The endogenous opioid system is actually multiple systems marked by distinct distributions of multiple endogenous opioid peptides and opiate receptor subtypes, as well as varying accessibility to drug administration. Future challenges in depression may rely upon the development of opiate agonists and antagonists with preferential binding to opiate receptor subtypes and preferential distributions to stress particular endogenous opioid systems. Opiate peptide challenges may well be administered intrathecally to overcome the blood-brain barrier. Opiate antagonist challenges will rely upon increasing doses of naloxone, up to 10 mg/kg, in order to increase the range of blocked endogenous opiate systems. Chronic administration of challenges has been a seldom used strategy but may be important in evaluation of the physiology of sensitization and tolerance to pleasure in affective illness.
内源性阿片系统的发现之后，迅速开展了动物研究，这些研究表明该系统在神经内分泌调节和行为方面具有重要性。情感性疾病中这些功能的异常表明，评估阿片激动剂或拮抗剂临床给药后的行为和激素反应，可能会产生与抑郁症的发病机制、诊断和治疗相关的信息。然而，最初的双盲对照临床研究几乎没有证据支持阿片系统参与情感性疾病的这一观点。阿片激动剂的急性给药有时会在抑郁症中产生轻微的抗抑郁反应，并且纳洛酮偶尔被报道对躁狂症有益。然而，几乎没有证据表明这些反应是情感性疾病所特有的。有报道称抑郁症患者对吗啡给药的催乳素反应降低，但这并非抑郁症中阿片系统功能障碍的直接证据，因为此前已报道抑郁症患者对其他刺激的催乳素反应异常。内源性阿片系统实际上是多个系统，其特征是多种内源性阿片肽和阿片受体亚型的分布不同，以及药物给药的可及性各异。抑郁症未来面临的挑战可能依赖于开发与阿片受体亚型具有优先结合且优先分布于特定内源性阿片系统的阿片激动剂和拮抗剂。阿片肽刺激很可能通过鞘内给药来克服血脑屏障。阿片拮抗剂刺激将依赖于增加纳洛酮的剂量，最高可达10mg/kg，以扩大被阻断的内源性阿片系统的范围。长期给予刺激一直是一种很少使用的策略，但在评估情感性疾病中对愉悦的致敏和耐受生理学方面可能很重要。
