Kimes A S, Bell J A, London E D
Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224.
Neuroscience. 1990;34(3):633-44. doi: 10.1016/0306-4522(90)90170-9.
The effect of two doses of clonidine on regional cerebral metabolic rates for glucose were measured during morphine withdrawal in rats. In the first study, 0 or 200 micrograms/kg clonidine was administered to rats subjected to naloxone-precipitated morphine withdrawal (naloxone, 0.5 mg/kg, s.c.), and to non-dependent control rats. In a second study of similar design, 0 or 20 micrograms/kg clonidine were administered. Withdrawal signs in rats subjected to naloxone-precipitated morphine withdrawal and receiving 0, 20 or 200 micrograms/kg clonidine were also assessed. Naloxone-precipitated morphine withdrawal stimulated regional cerebral metabolic rates for glucose (59 of 83 regions in study no. 1; 73 of 83 regions in study no. 2). At 200 micrograms/kg, clonidine attenuated this effect (33 of 59 regions). Although 200 micrograms/kg clonidine directly suppressed regional cerebral metabolic rates for glucose in many regions (significant main effect of clonidine), it attenuated the naloxone-precipitated morphine withdrawal effect specifically in the lateral septal nucleus, medial habenula, subiculum and gracile nucleus (significant interactions between clonidine and morphine withdrawal). The 20 micrograms/kg dose of clonidine had no statistically significant effect. In behavioral experiments, both doses of clonidine diminished withdrawal in that there was no diarrhea, fewer wet-dog shakes and less abnormal posturing. However, locomotion, grooming and jumping were increased by clonidine. Most of these effects were statistically significant only with the 200 micrograms/kg dose. The results of these studies show that clonidine reduces morphine withdrawal-induced increases in regional cerebral metabolic rates for glucose in many brain regions, irrespective of the distribution of alpha 2-adrenoceptors. Although clonidine has been thought to ameliorate morphine withdrawal by actions primarily at the locus coeruleus and central amygdala, it may play a major role in other regions as well.
在大鼠吗啡戒断期间，测量了两剂量可乐定对局部脑葡萄糖代谢率的影响。在第一项研究中，给接受纳洛酮诱发吗啡戒断的大鼠（皮下注射0.5mg/kg纳洛酮）以及非依赖性对照大鼠注射0或200μg/kg可乐定。在第二项设计相似的研究中，注射0或20μg/kg可乐定。还评估了接受0、20或200μg/kg可乐定的纳洛酮诱发吗啡戒断大鼠的戒断症状。纳洛酮诱发的吗啡戒断刺激了局部脑葡萄糖代谢率（在研究1的83个区域中有59个；在研究2的83个区域中有73个）。在200μg/kg时，可乐定减弱了这种作用（59个区域中的33个）。尽管200μg/kg可乐定在许多区域直接抑制了局部脑葡萄糖代谢率（可乐定的显著主效应），但它在外侧隔核、内侧缰核、下托和薄束核中特异性地减弱了纳洛酮诱发的吗啡戒断效应（可乐定与吗啡戒断之间的显著交互作用）。20μg/kg剂量的可乐定没有统计学上的显著作用。在行为实验中，两剂量的可乐定都减轻了戒断症状，即没有腹泻、湿狗样抖动减少且异常姿势减少。然而，可乐定增加了运动、梳理毛发和跳跃行为。这些效应大多数仅在200μg/kg剂量时具有统计学显著性。这些研究结果表明，无论α2-肾上腺素能受体的分布如何，可乐定均可降低吗啡戒断诱导的许多脑区局部脑葡萄糖代谢率的升高。尽管一直认为可乐定主要通过作用于蓝斑和中央杏仁核来改善吗啡戒断，但它在其他区域可能也起主要作用。
