Stengaard-Pedersen K, Schou M
Acta Pharmacol Toxicol (Copenh). 1985;56 Suppl 1:170-9. doi: 10.1111/j.1600-0773.1985.tb02509.x.
A brief review is given of clinical and experimental evidence supporting the notion that opioid peptides and opioid receptors play a role for the regulation of mood and activity, and that they could be involved in the pathophysiology of affective illness and the action of antimanic and antidepressant treatment modalities. We have carried out in vitro and in vivo studies on the effects of desipramine and lithium on opioid receptors in rat brain. In vitro desipramine inhibited the binding of 3H-enkephalinamide to neuronal membranes (P2-fractions) through mechanisms not yet known. Treatment with desipramine in vivo (10 mg/kg body weight/day) caused a down-regulation of 3H-enkephalinamide binding in the basal ganglia and the hippocampus, while no effects could be observed in the cerebral cortex and the rest of the forebrain. In vitro addition of lithium inhibited enkephalin binding to opioid receptors through a reduction in the number of binding sites, while the affinity remained unchanged or was changed only slightly. Treatment with lithium in vivo for three weeks with lithium doses providing serum lithium concentrations of about 1 mM also caused a down-regulation in the number of opioid binding sites in the cerebral cortex, the hippocampus, and the basal ganglia, while no changes could be observed in affinity. The studies suggest that desipramine and lithium, both effective in the treatment of manic-depressive illness, may share certain actions on opioid receptors in the brain.
本文简要回顾了临床和实验证据，这些证据支持阿片肽和阿片受体在情绪和活动调节中发挥作用的观点，以及它们可能参与情感性疾病的病理生理学和抗躁狂及抗抑郁治疗方式的作用。我们已经对去甲丙咪嗪和锂对大鼠脑内阿片受体的影响进行了体外和体内研究。在体外，去甲丙咪嗪通过尚未明确的机制抑制3H-脑啡肽酰胺与神经元膜（P2组分）的结合。体内给予去甲丙咪嗪（10mg/kg体重/天）导致基底神经节和海马中3H-脑啡肽酰胺结合下调，而在大脑皮层和前脑的其他部分未观察到影响。在体外添加锂通过减少结合位点数量来抑制脑啡肽与阿片受体的结合，而亲和力保持不变或仅略有变化。体内用锂治疗三周，锂剂量使血清锂浓度达到约1mM，也导致大脑皮层、海马和基底神经节中阿片结合位点数量下调，而亲和力未观察到变化。这些研究表明，对躁狂抑郁症均有效的去甲丙咪嗪和锂可能在脑内阿片受体上具有某些共同作用。
