Murphy N P, Onaka T, Brown C H, Leng G
Laboratory for Neuroendocrinology, Babraham Institute, Cambridge, U.K.
Neuroscience. 1997 Sep;80(2):567-77. doi: 10.1016/s0306-4522(97)00142-5.
During prolonged exposure to morphine, oxytocin neurons of the rat supraoptic nucleus develop dependence, shown by hyperexcitation following morphine withdrawal. The present study investigated the role of afferent projections to the supraoptic nucleus in this withdrawal excitation. Rats were made morphine-dependent by continuous intracerebroventricular infusion of morphine at increasing doses (up to 50 microg/h). On the sixth day, rats were anaesthetized with pentobarbitone and morphine withdrawal was precipitated by intraperitoneal injection of naloxone (5 mg/kg). Fos-immunoreactivity in the supraoptic nucleus, and also in the median preoptic nucleus, organum vasculosum of the lamina terminalis and subfornical organ, which project to the supraoptic nucleus, increased following morphine withdrawal. However, retrograde tracing from the supraoptic nucleus showed that, of the neurons in these regions which project to the supraoptic nucleus, only 0.4-7.1% expressed Fos in response to morphine withdrawal. Following morphine withdrawal, Fos-immunoreactivity was present in 39.2% and 19.8% of the tyrosine hydroxylase-immunoreactive neurons of the A1/C1 and A2/C2 cell groups. Of the cells in these regions identified as projecting to the supraoptic nucleus, 11.3% in the region of the A2 cell group and 12.7% in the region of the A1 cell group expressed Fos after morphine withdrawal. In a second study, monoamine release was measured in the supraoptic nucleus of urethane-anaesthetized morphine-dependent and -naive rats. Retrodialysis of naloxone (10[-5] M) into the supraoptic nucleus induced a small increase in plasma oxytocin concentration in morphine-dependent rats (13.5+/-4.8 pg/ml increase) but not in naive rats (1.2+/-5.9 pg/ml decrease), with no significant change in monoamine release in either morphine-dependent or -naive rats. Intravenous injection of naloxone (5 mg/kg) 1 h later produced a further significant increase in plasma oxytocin concentration in morphine-dependent rats concomitant with a significant increase in noradrenaline release from the supraoptic nucleus. Thus, morphine-withdrawal excitation of supraoptic oxytocin neurons occurs concurrently with a modestly increased activity of their input from the brainstem, and very little activation in other known inputs.
在长期接触吗啡的过程中，大鼠视上核的催产素神经元会产生依赖性，表现为吗啡戒断后出现过度兴奋。本研究调查了投射到视上核的传入神经在这种戒断兴奋中的作用。通过持续脑室内注射递增剂量（高达50微克/小时）的吗啡使大鼠产生吗啡依赖性。在第6天，用戊巴比妥麻醉大鼠，并通过腹腔注射纳洛酮（5毫克/千克）引发吗啡戒断。吗啡戒断后，视上核以及投射到视上核的视前正中核、终板血管器和穹窿下器中的Fos免疫反应性增加。然而，从视上核进行逆行追踪显示，在这些投射到视上核的区域中，只有0.4 - 7.1%的神经元在吗啡戒断时表达Fos。吗啡戒断后，A1/C1和A2/C2细胞群中39.2%和19.8%的酪氨酸羟化酶免疫反应性神经元存在Fos免疫反应性。在这些被确定为投射到视上核的区域中，A2细胞群区域的11.3%和A1细胞群区域的12.7%在吗啡戒断后表达Fos。在第二项研究中，测量了乌拉坦麻醉的吗啡依赖和未接触吗啡大鼠视上核中的单胺释放。将纳洛酮（10[-5] M）逆向透析到视上核中，在吗啡依赖大鼠中诱导血浆催产素浓度小幅升高（升高13.5±4.8皮克/毫升），而在未接触吗啡大鼠中则没有（降低1.2±5.9皮克/毫升），吗啡依赖和未接触吗啡大鼠的单胺释放均无显著变化。1小时后静脉注射纳洛酮（5毫克/千克），在吗啡依赖大鼠中导致血浆催产素浓度进一步显著升高，同时视上核去甲肾上腺素释放显著增加。因此，视上核催产素神经元的吗啡戒断兴奋与来自脑干的输入活动适度增加同时发生，而其他已知输入的激活非常少。
