Britton K T, Svensson T, Schwartz J, Bloom F E, Koob G F
Life Sci. 1984 Jan 9;34(2):133-9. doi: 10.1016/0024-3205(84)90583-6.
Previous work has shown that clonidine effectively suppresses many of the signs of opiate withdrawal. The present study was designed to test the hypothesis that the suppression of opiate withdrawal by clonidine is mediated by forebrain noradrenergic projections of the locus coeruleus. 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 subcutaneous implantation of one 75 mg silastic morphine pellet for three days followed by 3 more days with two additional 75 mg pellets. Following removal of the morphine pellet, withdrawal was precipitated in all rats by subcutaneous 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 coeruleus had no effect on withdrawal, nor did they affect the ameliorating action of clonidine. These results substantiate the observation that clonidine can effectively attenuate signs of opiate withdrawal in the rat, but fail to support the hypothesis that these effects are mediated by the forebrain projections of the locus coeruleus.
先前的研究表明，可乐定可有效抑制许多阿片戒断症状。本研究旨在验证以下假设：可乐定对阿片戒断的抑制作用是由蓝斑核的前脑去甲肾上腺素能投射介导的。将两组各24只大鼠分别进行去甲肾上腺素能背束的6-羟基多巴胺损伤（损伤组）或假手术、注射溶剂（假手术组）。所有大鼠通过皮下植入一枚75毫克的硅橡胶吗啡丸3天，然后再植入两枚75毫克的吗啡丸3天，从而使其对吗啡产生依赖。去除吗啡丸后，通过皮下注射4毫克/千克的纳洛酮使所有大鼠出现戒断反应。在戒断前10分钟用可乐定（0.1或0.2毫克/千克）预处理，与注射生理盐水的大鼠相比，戒断症状明显减轻；在假手术组和损伤组中，这种效果同样显著。蓝斑核损伤对戒断反应没有影响，也不影响可乐定的改善作用。这些结果证实了可乐定可有效减轻大鼠阿片戒断症状的观察结果，但未能支持这些作用是由蓝斑核的前脑投射介导的这一假设。
