Russell J A, Neumann I, Landgraf R
Department of Physiology, University Medical School, Edinburgh, United Kingdom.
J Neurosci. 1992 Mar;12(3):1024-32. doi: 10.1523/JNEUROSCI.12-03-01024.1992.
The effects of naloxone on the release of oxytocin and vasopressin in discrete brain areas were investigated in control and morphine-tolerant/dependent female rats anesthetized with urethane. Two or three consecutive push-pull perfusates were collected for 30-40 min each and the peptide contents measured by radioimmunoassay; naloxone (5 mg/kg, i.v.) was given after the first perfusion. In control rats, naloxone did not increase oxytocin release from any of the regions studied: mediolateral septum, dorsal hippocampus, nucleus of tractus solitarius, or supraoptic nucleus. After naloxone, vasopressin release was approximately doubled in the nucleus of tractus solitarius (p less than 0.05), indicating endogenous opioid inhibition of vasopressin release. Naloxone increased oxytocin concentration in the circulation 3.7-fold (p less than 0.001) but did not affect vasopressin secretion. In rats made morphine tolerant/dependent by intracerebroventricular infusion of morphine for 5 d, oxytocin and vasopressin release in the perfused brain was initially similar to that in control rats, indicating tolerance to any initial morphine effects. In these rats, naloxone increased oxytocin release in the septum threefold relative to control rats (p less than 0.02) but did not alter oxytocin release in hippocampus or nucleus of tractus solitarius. Thus, the oxytocin neurons projecting to septum can develop morphine dependence and may be inhibited acutely by opioids acting via mu-receptors. The results indicate morphine acts selectively on oxytocin neurons projecting to mediolateral septum compared with other central projection areas and compared with centrally projecting vasopressin neurons. In the supraoptic nucleus, naloxone increased oxytocin release 2.3-fold (from 9.2 +/- 3.1 pg/30 min) and increased oxytocin release from axons of these neurons fivefold (from 7.8 +/- 3.2 pg/30 min). Naloxone had no significant effect on vasopressin release from any of the central sites, or on vasopressin secretion into blood, although oxytocin secretion was increased 36-fold (from 17.2 +/- 2.6 pg/ml; p less than 0.001), confirming dependence of magnocellular oxytocin neurons. The central processes of magnocellular supraoptic neurons may be a major source of central oxytocin released during morphine withdrawal.
在使用乌拉坦麻醉的对照和吗啡耐受/依赖雌性大鼠中，研究了纳洛酮对离散脑区中催产素和血管加压素释放的影响。连续收集两到三次推挽灌流液，每次30 - 40分钟，并通过放射免疫测定法测量肽含量；在第一次灌流后静脉注射纳洛酮（5毫克/千克）。在对照大鼠中，纳洛酮并未增加所研究的任何区域（内侧隔区、背侧海马体、孤束核或视上核）的催产素释放。注射纳洛酮后，孤束核中的血管加压素释放量增加了约一倍（p < 0.05），表明内源性阿片类物质对血管加压素释放有抑制作用。纳洛酮使循环中的催产素浓度增加了3.7倍（p < 0.001），但不影响血管加压素的分泌。通过脑室内注射吗啡5天使大鼠产生吗啡耐受/依赖后，灌流脑区中的催产素和血管加压素释放最初与对照大鼠相似，表明对吗啡的任何初始作用产生了耐受性。在这些大鼠中，与对照大鼠相比，纳洛酮使隔区的催产素释放增加了三倍（p < 0.02），但未改变海马体或孤束核中的催产素释放。因此，投射到隔区的催产素神经元可能会产生吗啡依赖性，并且可能会被通过μ受体起作用的阿片类物质急性抑制。结果表明，与其他中枢投射区域以及中枢投射的血管加压素神经元相比，吗啡对投射到内侧隔区的催产素神经元具有选择性作用。在视上核中，纳洛酮使催产素释放增加了2.3倍（从9.2±3.1皮克/30分钟增加到），并使这些神经元轴突的催产素释放增加了五倍（从7.8±3.2皮克/30分钟增加到）。纳洛酮对任何中枢部位的血管加压素释放或血管加压素分泌到血液中均无显著影响，尽管催产素分泌增加了36倍（从17.2±2.6皮克/毫升增加到；p < 0.001），证实了大细胞催产素神经元的依赖性。大细胞视上神经元的中枢突可能是吗啡戒断期间中枢释放的催产素的主要来源。
