Blackburn-Munro G, Brown C H, Neumann I D, Landgraf R, Russell J A
Department of Biomedical Sciences, University Medical School, EH8 9XD, Edinburgh, United Kingdom.
Neuropharmacology. 2000 Jul 10;39(9):1596-607. doi: 10.1016/s0028-3908(99)00232-4.
We investigated whether the full expression of morphine withdrawal excitation by supraoptic nucleus (SON) oxytocin neurones is a property of the neurones themselves or a partial function of their afferent inputs, by interrupting synaptic input activity via central administration of the L-type Ca(2+) channel blocker verapamil. In morphine-dependent rats, withdrawal-induced release of oxytocin from the posterior pituitary was suppressed by prior administration of intracerebroventricular (i.c.v.) verapamil (160 microg), as was release of oxytocin within the SON measured by microdialysis. During morphine withdrawal the increased electrical activity of SON neurones was also reduced both by i.c.v. verapamil and microdialysis application of verapamil or nifedipine into the SON. Oxytocin secretion evoked by electrical stimulation of the pituitary stalk was unaffected by i.c.v. verapamil suggesting a central site of action. To determine whether the inhibitory actions of verapamil were specific to morphine withdrawal, we also investigated the effects of verapamil on other oxytocin-secreting stimuli. I.C.V. verapamil given to morphine-naïve rats abolished pituitary oxytocin release in response to activation of brainstem or rostral excitatory inputs by cholecystokinin (20 microg kg(-1), i.v.) and 1.5 M saline (4 ml kg(-1), i.p.) respectively, whilst in lactating rats, i.c.v. verapamil reduced suckling-induced release of oxytocin within the SON. These results suggest that verapamil has a central site of action on stimulated oxytocin release (including an action within the SON) and that both pre and post-synaptic L-type Ca(2+) channels are required for the full expression of morphine withdrawal in SON oxytocin neurones.
我们通过经中枢给予L型钙通道阻滞剂维拉帕米来中断突触输入活动，研究视上核（SON）催产素神经元对吗啡戒断兴奋的完全表达是神经元自身的特性，还是其传入输入的部分功能。在吗啡依赖的大鼠中，预先给予脑室内（i.c.v.）维拉帕米（160微克）可抑制戒断诱导的垂体后叶催产素释放，通过微透析测量的SON内催产素释放也受到抑制。在吗啡戒断期间，i.c.v.维拉帕米以及向SON内微透析应用维拉帕米或硝苯地平，均可降低SON神经元增加的电活动。垂体柄电刺激诱发的催产素分泌不受i.c.v.维拉帕米影响，提示其作用位点在中枢。为了确定维拉帕米的抑制作用是否对吗啡戒断具有特异性，我们还研究了维拉帕米对其他催产素分泌刺激的影响。分别给未接触过吗啡的大鼠i.c.v.维拉帕米，可消除胆囊收缩素（20微克·千克⁻¹，静脉注射）和1.5 M盐水（4毫升·千克⁻¹，腹腔注射）激活脑干或 Rostral 兴奋性输入所引起的垂体催产素释放，而在哺乳期大鼠中，i.c.v.维拉帕米可减少SON内哺乳诱导的催产素释放。这些结果表明，维拉帕米对刺激的催产素释放具有中枢作用位点（包括在SON内的作用），并且突触前和突触后L型钙通道对于SON催产素神经元中吗啡戒断的完全表达都是必需的。
