Russell J A, Pumford K M, Bicknell R J
Department of Physiology, University Medical School, Edinburgh, UK.
Neuroendocrinology. 1992 Feb;55(2):183-92. doi: 10.1159/000126113.
Virgin female or lactating rats were given infusion into a lateral cerebral ventricle (i.c.v.) of either morphine to produce tolerance and dependence or vehicle from a subcutaneous osmotic minipump for 5 days, then they were anaesthetized with urethane. In virgins either an electrolytic or sham lesion of the region anterior and ventral to the third ventricle (AV3V region) was made. Initial blood plasma concentrations of oxytocin, measured by radioimmunoassay were similar in i.c.v. morphine- and i.c.v. vehicle-infused rats (20.6 +/- 2.7 and 19.0 +/- 4.3 pg/ml, respectively). Naloxone (5 mg/kg i.v.) significantly increased oxytocin secretion in all groups for at least 60 min; oxytocin concentration at 6 min after naloxone was in the order: sham-lesioned i.c.v. morphine group (mean 1,839 +/- 809 pg/ml, n = 6), greater than AV3V-lesioned i.c.v. morphine group (326 +/- 65 pg/ml, n = 6), = sham-lesioned i.c.v. vehicle group (251 +/- 66 pg/ml, n = 6), greater than AV3V-lesioned i.c.v. vehicle group (47.2 +/- 12.4 pg/ml, n = 6). Thus in both intact and lesioned rats naloxone increased oxytocin secretion much more in morphine-dependent rats than in the respective controls; in both morphine-naive and morphine-dependent rats, the AV3V lesion reduced the effect of naloxone with respect to plasma oxytocin concentration, but not with respect to the increase relative to the lower prenaloxone concentrations in the lesioned rats (prenaloxone values in the lesioned rats were: i.c.v. vehicle group, 15.8 +/- 6.8 pg/ml; i.c.v. morphine group, 24.3 +/- 7.8 pg/ml; and in the sham-lesioned rats: i.c.v. vehicle group, 67.3 +/- 31.2 pg/ml, i.c.v. morphine group, 65.5 +/- 15.0 pg/ml). Thus the AV3V region is not essential for withdrawal excitation of oxytocin secretion in morphine-dependent rats. In lactating morphine-dependent rats, i.c.v. infusion of the angiotension II antagonist saralasin (2.5 micrograms/min) decreased plasma oxytocin concentration after 10 min (5.7 +/- 1.1 pg/ml, n = 7 vs. 13.2 +/- 3.2 pg/ml, n = 8), but did not prevent naloxone-provoked excitation of oxytocin secretion, measured by radioimmunoassay (6 min after naloxone in the i.c.v. saralasin group 402.8 +/- 124.5 pg/ml, n = 7 vs, in controls, 1,009 +/- 382 pg/ml, n = 7) or assessed by continuous recording of intramammary pressure. These results indicate that centrally acting angiotensin II is not an important mediator of naloxone-induced oxytocin hypersecretion in morphine-dependent rats.(ABSTRACT TRUNCATED AT 400 WORDS)
将未生育的雌性或泌乳期大鼠通过皮下渗透微型泵向侧脑室（脑室内）注入吗啡以产生耐受性和依赖性，或注入赋形剂，持续5天，然后用乌拉坦麻醉。对于未生育的大鼠，对第三脑室前腹侧区域（AV3V区域）进行电解损伤或假损伤。通过放射免疫测定法测得的催产素初始血浆浓度在脑室内注入吗啡的大鼠和脑室内注入赋形剂的大鼠中相似（分别为20.6±2.7和19.0±4.3 pg/ml）。纳洛酮（5 mg/kg静脉注射）在所有组中至少60分钟内显著增加催产素分泌；纳洛酮注射后6分钟时催产素浓度顺序为：假损伤脑室内注入吗啡组（平均1839±809 pg/ml，n = 6），大于AV3V损伤脑室内注入吗啡组（326±65 pg/ml，n = 6），=假损伤脑室内注入赋形剂组（251±66 pg/ml，n = 6），大于AV3V损伤脑室内注入赋形剂组（47.2±12.4 pg/ml，n = 6）。因此，在完整和损伤的大鼠中，纳洛酮在吗啡依赖大鼠中比在各自的对照组中更能增加催产素分泌；在未接触过吗啡和吗啡依赖的大鼠中，AV3V损伤相对于血浆催产素浓度降低了纳洛酮的作用，但相对于损伤大鼠中纳洛酮给药前较低浓度的增加幅度而言则没有降低（损伤大鼠中纳洛酮给药前的值为：脑室内注入赋形剂组，15.8±6.8 pg/ml；脑室内注入吗啡组，24.3±7.8 pg/ml；在假损伤大鼠中：脑室内注入赋形剂组，67.3±31.2 pg/ml，脑室内注入吗啡组，65.5±15.0 pg/ml）。因此，AV3V区域对于吗啡依赖大鼠中催产素分泌的戒断兴奋并非必不可少。在泌乳期吗啡依赖大鼠中，脑室内注入血管紧张素II拮抗剂沙拉新（2.5微克/分钟）10分钟后降低了血浆催产素浓度（5.7±1.1 pg/ml，n = 7对比13.2±3.2 pg/ml，n = 8），但并未阻止通过放射免疫测定法（纳洛酮注射后6分钟，脑室内注入沙拉新组为402.8±124.5 pg/ml，n = 7对比对照组为1009±382 pg/ml，n = 7）或通过连续记录乳腺内压力评估的纳洛酮诱发的催产素分泌兴奋。这些结果表明，中枢作用的血管紧张素II并非吗啡依赖大鼠中纳洛酮诱导的催产素分泌过多的重要介质。（摘要截短至400字）
