Sheward W J, Coombes J E, Bicknell R J, Fink G, Russell J A
MRC Brain Metabolism Unit, University Department of Pharmacology, Edinburgh.
J Endocrinol. 1990 Jan;124(1):141-50. doi: 10.1677/joe.0.1240141.
The effects of morphine dependence and abrupt opiate withdrawal on the release of oxytocin and corticotrophin-releasing factor-41 (CRF-41) into hypophysial portal vessel blood in rats anaesthetized with urethane were investigated. Adult female Sprague-Dawley rats were made dependent upon morphine by intracerebroventricular infusion of morphine for 5 days; abrupt opiate withdrawal was induced by injection of the opiate antagonist naloxone. The basal concentrations of oxytocin in portal or peripheral plasma from morphine-dependent rats did not differ significantly from those in control, vehicle-infused rats. In rats in which the pituitary gland was not removed after stalk section, the i.v. injection of naloxone hydrochloride (5 mg/kg) resulted in a large and sustained increase in the concentration of oxytocin in both portal and peripheral plasma in control and morphine-dependent rats. The i.v. injection of naloxone resulted in a threefold increase in the secretion of oxytocin into portal blood in acutely hypophysectomized rats infused with morphine, but did not alter oxytocin secretion in vehicle-infused hypophysectomized rats. The concentration of oxytocin in peripheral plasma in both vehicle- and morphine-infused hypophysectomized rats was at the limit of detection of the assay and was unchanged by the administration of naloxone. There were no significant differences in the secretion of CRF-41 into portal blood in vehicle- or morphine-infused hypophysectomized rats either before or after the administration of naloxone. These data show that, as for oxytocin release from the neurohypophysis into the systemic circulation, the mechanisms which regulate oxytocin release into the portal vessel blood can also be made morphine dependent. The lack of effect of morphine or naloxone on the release of CRF-41 or other stress neuro-hormones suggests that the effect of opiate dependence and withdrawal is selective for oxytocin and is not simply a non-specific response to 'stress'.
研究了吗啡依赖和阿片类药物突然戒断对用乌拉坦麻醉的大鼠垂体门脉血管血中催产素和促肾上腺皮质激素释放因子41（CRF - 41）释放的影响。成年雌性Sprague - Dawley大鼠通过脑室内注入吗啡5天使其对吗啡产生依赖；通过注射阿片类拮抗剂纳洛酮诱导阿片类药物突然戒断。吗啡依赖大鼠门脉或外周血浆中催产素的基础浓度与对照的、注入赋形剂的大鼠相比无显著差异。在垂体柄切断后未切除垂体的大鼠中，静脉注射盐酸纳洛酮（5毫克/千克）导致对照和吗啡依赖大鼠的门脉和外周血浆中催产素浓度大幅且持续升高。静脉注射纳洛酮使注入吗啡的急性垂体切除大鼠向门脉血中分泌的催产素增加了三倍，但未改变注入赋形剂的垂体切除大鼠的催产素分泌。注入赋形剂和吗啡的垂体切除大鼠外周血浆中催产素的浓度处于该检测方法的检测极限，且纳洛酮给药后未发生变化。在注入赋形剂或吗啡的垂体切除大鼠中，无论给药前还是给药后，向门脉血中分泌CRF - 41均无显著差异。这些数据表明，对于神经垂体向体循环释放催产素而言，调节催产素向门脉血管血中释放的机制也可被吗啡依赖。吗啡或纳洛酮对CRF - 41或其他应激神经激素释放缺乏影响表明，阿片类药物依赖和戒断的作用对催产素具有选择性，并非简单的对“应激”的非特异性反应。
