Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia.
Minocycline suppresses morphine-induced respiratory depression, suppresses morphine-induced reward, and enhances systemic morphine-induced analgesia.
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DOI：
10.1016/j.bbi.2008.07.008
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发表时间：
2008-11
影响因子：
15.1
通讯作者：
Watkins, Linda R.
中科院分区：
文献类型：
--
作者：
Hutchinson, Mark R.;Northcutt, Alexis L.;Chao, Lindsey W.;Kearney, Jeffrey J.;Zhang, Yingning;Berkelhammer, Debra L.;Loram, Lisa C.;Rozeske, Robert R.;Bland, Sondra T.;Maier, Steven F.;Gleeson, Todd T.;Watkins, Linda R.
最近的数据表明，阿片类药物可以激活中枢神经系统(Glia)的免疫样细胞。这种阿片类药物诱导的胶质细胞激活与止痛作用减弱有关，这是由于促炎介质的释放。在这里，我们研究了假定的小胶质细胞抑制剂米诺环素是否会影响吗啡诱导的呼吸抑制和/或吗啡诱导的奖赏(条件性位置偏爱)。全身联合应用米诺环素可显著减轻吗啡引起的潮气量、分钟潮气量、吸气力和呼气力的降低，但不影响吗啡引起的呼吸频率的降低。米诺环素对呼吸抑制的减弱与米诺环素对吗啡诱导的血氧饱和度降低的显著减弱是平行的。米诺环素还可减弱吗啡条件性位置偏爱。米诺环素并不是简单地减少吗啡的所有作用，因为米诺环素联合应用显著增强了吗啡的镇痛作用。最后，吗啡剂量依赖地增加大鼠小胶质细胞系中环氧合酶-1基因的表达，这种作用被米诺环素剂量依赖地阻断。综上所述，这些数据支持吗啡可以以一种米诺环素抑制的方式直接激活小胶质细胞，并表明米诺环素敏感过程在吗啡诱导的呼吸抑制、奖赏和疼痛调制机制中起着关键作用。
Recent data suggest that opioids can activate immune-like cells of the central nervous system (glia). This opioid-induced glial activation is associated with decreased analgesia, owing to the release of proinflammatory mediators. Here we examine in rats whether the putative microglial inhibitor, minocycline, may affect morphine-induced respiratory depression and/or morphine-induced reward (conditioned place preference). Systemic co-administration of minocycline significantly attenuated morphine-induced reductions in tidal volume, minute volume, inspiratory force and expiratory force, but did not affect morphine-induced reductions in respiratory rate. Minocycline attenuation of respiratory depression was also paralleled with significant attenuation by minocycline of morphine-induced reductions in blood oxygen saturation. Minocycline also attenuated morphine conditioned place preference. Minocycline did not simply reduce all actions of morphine, as morphine analgesia was significantly potentiated by minocycline co-administration. Lastly, morphine dose-dependently increased cyclooxygenase-1 gene expression in a rat microglial cell line, an effect that was dose-dependently blocked by minocycline. Together, these data support that morphine can directly activate microglia in a minocycline-suppressible manner and suggest a pivotal role for minocycline-sensitive processes in the mechanisms of morphine-induced respiration depression, reward, and pain modulation.
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影响因子：
7.4
作者：
Ledeboer, A;Sloane, EM;Watkins, LR
通讯作者：
Watkins, LR
影响因子：
12.7
作者：
Biondo, B;Magagnin, S;Matturri, L
通讯作者：
Matturri, L
影响因子：
4.7
作者：
Festoff, Barry W.;Ameenuddin, Syed;Citron, Bruce A.
通讯作者：
Citron, Bruce A.
DOI：
10.1196/annals.1307.047
发表时间：
2004-01-01
期刊：
CURRENT STATUS OF DRUG DEPENDENCE / ABUSE STUDIES: CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE AND NEUROTOXICITY
影响因子：
--
作者：
Nakagawa, T;Satoh, M
通讯作者：
Satoh, M
影响因子：
2.7
作者：
Johnston, IN;Westbrook, RF
通讯作者：
Westbrook, RF