Leng G, Brown C H, Murphy N P, Onaka T, Russell J A
Department of Physiology, University Medical School, Edinburgh, UK.
Adv Exp Med Biol. 1995;395:95-104.
The nucleus tractus solitarii (NTS) projects directly to the oxytocin neurones of the supraoptic nucleus (SON), and relays afferent stimuli arising from the birth canal during parturition. About 80% of these projecting neurones are noradrenergic, and these same neurones are activated following systemic administration of cholecystokinin (CCK), which also results in an increased electrical and secretory activity in oxytocin neurones. Oxytocin release in response to CCK is abolished following selective neurotoxic destruction of these noradrenergic neurones. Oxytocin release following CCK (and that during parturition) is potently inhibited by morphine, which blocks the local noradrenaline release in the supraoptic nucleus. This acute opiate action involves presynaptic inhibition of the noradrenergic terminals, and occurs without marked suppression of the activity of noradrenergic cells in the NTS. During chronic exposure to morphine the oxytocin system becomes tolerant to, and dependent upon morphine. In the course of tolerance, oxytocin cell activation in response to CCK recovers from initial inhibition. However, the pathway that mediates this response does not appear to become dependent: the oxytocin cell response to CCK is unchanged by opiate withdrawal induced by naloxone, despite a large increase in the background electrical activity of oxytocin cells provoked by withdrawal. Nevertheless, expression of withdrawal excitation by oxytocin neurones is curiously contingent upon the activity of the noradrenergic input in that prior lesioning of this input has no effect upon the subsequent withdrawal excitation of oxytocin cells. Yet under urethane anaesthesia, acute pharmacological blockade of the noradrenergic input suppresses withdrawal. We discuss how these paradoxical observations might be reconciled, and note that the difference may be related to differing levels of tonic activity in the noradrenergic input. It is possible that dependence relies upon the input when it is there, but not when it is not.
孤束核（NTS）直接投射到视上核（SON）的催产素神经元，并传递分娩时来自产道的传入刺激。这些投射神经元中约80%是去甲肾上腺素能的，在全身给予胆囊收缩素（CCK）后，这些相同的神经元被激活，这也会导致催产素神经元的电活动和分泌活动增加。在这些去甲肾上腺素能神经元被选择性神经毒性破坏后，CCK引起的催产素释放被消除。CCK（以及分娩期间）引起的催产素释放被吗啡强烈抑制，吗啡会阻断视上核中局部去甲肾上腺素的释放。这种急性阿片作用涉及对去甲肾上腺素能终末的突触前抑制，并且在不显著抑制NTS中去甲肾上腺素能细胞活性的情况下发生。在长期接触吗啡期间，催产素系统对吗啡产生耐受性并依赖于吗啡。在耐受过程中，催产素细胞对CCK的激活从最初的抑制中恢复。然而，介导这种反应的途径似乎并未变得依赖：尽管纳洛酮诱导的阿片戒断会使催产素细胞的背景电活动大幅增加，但催产素细胞对CCK的反应在阿片戒断后并未改变。尽管如此，催产素神经元的戒断兴奋表达奇怪地取决于去甲肾上腺素能输入的活动，因为该输入的先前损伤对催产素细胞随后的戒断兴奋没有影响。然而，在乌拉坦麻醉下，去甲肾上腺素能输入的急性药理学阻断会抑制戒断反应。我们讨论了如何调和这些矛盾的观察结果，并指出差异可能与去甲肾上腺素能输入中不同水平的紧张性活动有关。有可能依赖性在有该输入时依赖于它，但在没有时则不然。
