PARTICIPATION OF DIFFERENT BRAIN-REGIONS IN THE ANTINARCOTIC WITHDRAWAL ACTION OF CLONIDINE IN THE DEPENDENT RAT
PARTICIPATION OF DIFFERENT BRAIN-REGIONS IN THE ANTINARCOTIC WITHDRAWAL ACTION OF CLONIDINE IN THE DEPENDENT RAT
复制标题
DOI：
10.1016/0006-8993(90)91083-s
复制
发表时间：
1990-04-09
期刊：
影响因子：
2.9
通讯作者：
BUCCAFUSCO, JJ
中科院分区：
文献类型：
--
作者：
BUCCAFUSCO, JJ
通过测量戒断后平均动脉压（MAP）、心率和一些特征性行为变化来定量吗啡依赖大鼠的纳洛酮促戒断反应。鞘内注射可乐定预处理可显著减少大多数戒断自主神经症状，包括MAP增加、流涎和血泪症，但对行为体征、身体抖动、逃跑尝试或牙齿打颤没有影响。中枢静脉注射可乐定也减轻了戒断的自主神经症状。可乐定给药的两种途径之间的两个差异是关于（1）后肢踢的程度，其中i.t.，但i. c. v.给药不能有效减轻该症状;和（2）i. c. v.，但不是IT。可乐定能显著降低腹泻的发生率。相反，脑池内（延髓水平）注射可乐定对停药后MAP的增加没有影响，对其他症状的抑制作用仅包括流涎和腹泻。因此，鞘内注射可乐定的作用不是由于药物重新分布到更高的中心。鞘内直接注射纳洛酮也可引起吗啡依赖大鼠的戒断反应。在这种情况下，鞘内可乐定预处理并没有抑制停药后MAP的增加。这些结果与大鼠吗啡戒断的自主神经和行为症状的脊髓成分一致。可乐定的抗戒断反应至少部分通过脊髓作用介导。然而，可乐定的这种脊髓抗戒断作用对源自脊髓上中枢的戒断反应具有选择性。
The naloxone-precipitated withdrawal response in morphine dependent rats was quantitated by measuring the post-withdrawal increase in mean arterial pressure (MAP), heart rate and several characteristic behavioral changes. Pretreatment with intrathecal injection of clonidine produced a significant reduction in most of the autonomic symptoms of withdrawal, including the increase in MAP, salivation, and chromodacryorrhea, but did not effect the behavioral signs, body shakes, escape attempts or teeth chattering. Central i.c.v. injection of clonidine also reduced the autonomic symptoms of withdrawal. Two differences between the two routes of clonidine administration were with respect to (1) the degree of hind limb kicking where i.t., but not i.c.v. administration was effective at reducing this symptom; and (2) i.c.v., but not i.t. clonidine was effective in significantly reducing the incidence of diarrhea. In contrast, intracisternal (medullary level) injection of clonidine was without effect on the post-withdrawal increase in MAP, and inhibitory effects on the other symptoms included only salivation and diarrhea. Thus the effect of clonidine following intrathecal injection was not due to redistribution of drug to higher centers. Direct intrathecal injection of naloxone also precipitated withdrawal in morphine dependent rats. In this case, intrathecal pretreatment with clonidine did not inhibit the post-withdrawal increase in MAP. These results are consistent with a spinal component for the autonomic and behavioral symptoms of morphine withdrawal in the rat. Clonidine''s antiwithdrawal response is mediated at least in part through a spinal action. However, this spinal antiwithdrawal action of clonidine is selective for withdrawal responses which originate from supraspinal centers.