DORSAL NORADRENERGIC BUNDLE LESIONS FAIL TO ALTER OPIATE WITHDRAWAL OR SUPPRESSION OF OPIATE WITHDRAWAL BY CLONIDINE
DORSAL NORADRENERGIC BUNDLE LESIONS FAIL TO ALTER OPIATE WITHDRAWAL OR SUPPRESSION OF OPIATE WITHDRAWAL BY CLONIDINE
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DOI：
10.1016/0024-3205(84)90583-6
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发表时间：
1984-01-01
期刊：
影响因子：
6.1
通讯作者：
KOOB, GF
中科院分区：
文献类型：
--
作者：
BRITTON, KT;SVENSSON, T;KOOB, GF
可乐定有效地抑制了阿片类药物戒断的许多迹象。这种抑制可能是介导的前脑去甲肾上腺素能投射的蓝斑。对两组各24只大鼠进行背侧去甲肾上腺素能神经束的6-羟基多巴胺损伤（损伤组）或假手术、溶媒注射（假手术组）。所有大鼠通过皮下注射吗啡产生依赖。植入一个75 mg硅橡胶吗啡丸3天，然后再植入另外2个75 mg丸3天。移除吗啡颗粒后，通过s.c.注射4 mg/kg纳洛酮。与盐水注射大鼠相比，可乐定（0.1或0.2 mg/kg）在戒断前10 min预处理可显著减弱戒断体征;这种效应在假手术组和病变组中同样显著。蓝斑的病变对戒断没有影响，也不影响可乐定的改善作用。可乐定能有效地减轻大鼠阿片戒断症状，但这种作用可能不是由蓝斑的前脑投射介导的。
Clonidine effectively suppresses many of the signs of opiate withdrawal. This suppression may be mediated by forebrain noradrenergic projections of the locus ceruleus. Two groups of 24 rats each were subjected to either a 6-hydroxydopamine lesion of the dorsal noradrenergic bundle (Lesion group) or a sham, vehicle injection (Sham group). All rats were made dependent on morphine by s.c. implantation of one 75 mg silastic morphine pellet for 3 days followed by 3 more days with 2 additional 75 mg pellets. Following removal of the morphine pellet, withdrawal was precipitated in all rats by s.c. injection of 4 mg/kg of naloxone. Pretreatment 10 min before withdrawal with clonidine (0.1 or 0.2 mg/kg) produced a significant attenuation of withdrawal signs as compared to saline injected rats; this effect was equally significant in both sham and lesion groups. Lesions of the locus ceruleus had no effect on withdrawal, nor did they affect the ameliorating action of clonidine. Evidently clonidine can effectively attenuate signs of opiate withdrawal in the rat, but these effects may not be mediated by the forebrain projections of the locus coeruleus.