Wehrenberg W B, McNicol D, Wardlaw S L, Frantz A G, Ferin M
Endocrinology. 1981 Aug;109(2):544-7. doi: 10.1210/endo-109-2-544.
The present experiments were performed to determine the site of action (hypothalamic or hypophyseal) and the mechanism (dopaminergic or serotonergic) by which morphine increases PRL in monkeys (Macaca mulatta and Macaca nemestrina). To determine the site of action, 9 mg morphine were injected iv to four intact and four pituitary stalk-sectioned monkeys. PRL concentrations rose significantly (P less than 0.01) from less than 5 ng/ml to an average maximum value of 208 +/- 20 ng/ml at 15 min in intact animals, but remained unchanged in pituitary stalk-sectioned animals. There was a significant reduction (P less than 0.01) of this response in intact monkeys that received 5 mg L-dopa, iv, 5 min before the morphine stimulus. In these animals, PRL only rose to 100 +/- 46 ng/ml. In contrast, the PRL response in four monkeys pretreated with 5 or 20 mg methysergide, iv (a serotonin receptor blocker), 5 min before the opiate stimulus was not different from in controls. Likewise, the daily administration of 100 mg p-chlorophenylalanine, sc (a serotonin synthesis blocker), for 6 days failed to alter the PRL response to morphine. These data suggest that opiates increase PRL via a neural site of action and that the mechanism may involve dopaminergic but not serotonergic pathways.
进行本实验是为了确定吗啡使猕猴（恒河猴和豚尾猴）催乳素升高的作用部位（下丘脑或垂体）及其机制（多巴胺能或血清素能）。为确定作用部位，给4只完整的和4只垂体柄横断的猕猴静脉注射9毫克吗啡。完整动物体内催乳素浓度在15分钟时从低于5纳克/毫升显著升高（P<0.01）至平均最高值208±20纳克/毫升，但垂体柄横断的动物体内催乳素浓度保持不变。在吗啡刺激前5分钟静脉注射5毫克左旋多巴的完整猕猴中，这种反应显著降低（P<0.01）。在这些动物中，催乳素仅升至100±46纳克/毫升。相比之下，在阿片类刺激前5分钟静脉注射5或20毫克美西麦角（一种血清素受体阻滞剂）预处理的4只猕猴中，催乳素反应与对照组无差异。同样，连续6天皮下注射100毫克对氯苯丙氨酸（一种血清素合成阻滞剂）也未能改变催乳素对吗啡的反应。这些数据表明，阿片类药物通过神经作用部位升高催乳素，其机制可能涉及多巴胺能而非血清素能途径。
