TOLERANCE OF LOCUS COERULEUS NEURONS TO MORPHINE AND SUPPRESSION OF WITHDRAWAL RESPONSE BY CLONIDINE
TOLERANCE OF LOCUS COERULEUS NEURONS TO MORPHINE AND SUPPRESSION OF WITHDRAWAL RESPONSE BY CLONIDINE
复制标题
DOI：
10.1038/276186a0
复制
发表时间：
1978-01-01
期刊：
影响因子：
64.8
通讯作者：
AGHAJANIAN, GK
中科院分区：
文献类型：
--
作者：
AGHAJANIAN, GK
蓝斑去甲肾上腺素能神经元(LC；参考文献A6)1)被全身或局部注射肾上腺素能激动剂2-5、阿片6、7和脑啡肽8，9所抑制。LC的肾上腺素能受体属于突触前或α2类型5，似乎介导对复发性LC侧支10和来自下脑干4、11的肾上腺素输入的抑制反应。除了肾上腺素能受体，位于LC 12、13的阿片受体可能介导位于LC 14-16神经末梢的内源性阿片类物质(脑啡肽和脑啡肽)的作用。最近，可乐定被报道抑制阿片类物质(脑啡肽和β-内啡肽)的活动。最近，可乐定被报道抑制阿片类物质(脑啡肽和脑啡肽)的作用。在此基础上，作者认为阿片戒断综合征可能部分是由于受α-2肾上腺素受体和阿片受体共同调节的LC等区去甲肾上腺素能神经元活动增加所致。在这方面，有趣的是，阻断α2肾上腺素受体并加速LC神经元4，5放电的药物哌咯烷会产生阿片类药物戒断时出现的许多症状(如焦虑和高血压)18。本研究采用单细胞记录和微离子电泳法，建立了LC细胞对吗啡抑制效应的耐受性、纳洛酮诱导的吗啡依赖动物LC神经元放电的戒断激活以及可乐定通过非阿片受体抑制LC神经元戒断的能力。
NORADRENERGIC neurones of the locus coeruleus (LC; A6 of ref. 1) are inhibited by the systemic or local administration of adrenergic agonists2–5, opiates6,7and enkephalins8,9. The adrenergic receptors of the LC, which are of the presynaptic orα2type5, seem to mediate inhibitory responses to recurrent LC collaterals10and adrenaline inputs from the lower brain stem4,11. In addition to adrenergic receptors, there are opiate receptors located in the LC12,13which presumably mediate the actions of endogenous opiate-like substances (enkephalins andβ-endorphin) located in nerve terminals within the LC14–16. Recently, clonidine, which is the most powerful of theα2agonists known to inhibit the firing of LC neurones3,5, has been reported to suppress the symptoms of opiate withdrawal in humans17. On this basis, the latter authors suggested that the opiate-withdrawal syndrome may be due in part to increased noradrenergic neuronal activity in areas such as the LC which are regulated by bothα2adrenoceptors and opiate receptors. In this connection, it is interesting that the drug piperoxane, which blocksα2adrenoceptors and accelerates the firing of LC neurones4,5produces many of the symptoms (such as anxiety and hypertension) seen in opiate withdrawal18. In the present study, single-cell recording and microiontophoretic techniques were used to establish the development of tolerance of LC cells to the depressant effects of morphine, naloxone-induced withdrawal activations of LC neuronal firing in morphine-dependent animals, and the ability of clonidine to suppress the withdrawal of LC neurones through a non-opiate receptor.