Periaqueductal gray neuroplasticity following chronic morphine varies with age: role of oxidative stress.
Periaqueductal gray neuroplasticity following chronic morphine varies with age: role of oxidative stress.
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DOI：
10.1016/j.neuroscience.2012.09.028
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发表时间：
2012-12-13
期刊：
影响因子：
3.3
通讯作者：
Commons, K. G.
中科院分区：
文献类型：
--
作者：
Bajic, D.;Berde, C. B.;Commons, K. G.
对吗啡的抗伤害性作用的耐受性的发展与腹外侧导水管周围灰质（vlPAG）内的网络以及单独的一氧化氮信号传导相关。此外，已知耐受性的基础机制随年龄而不同。在这项研究中，我们使用了大鼠模型的镇痛耐受吗啡在两个年龄，出生后第7天（PD）和成人，以确定在vlPAG的变化相关的一氧化氮信号产生的慢性吗啡暴露是年龄依赖性的。分析了三个药理学组：对照组、急性吗啡组和慢性吗啡组。每天两次皮下注射吗啡（10 mg/kg）或等体积生理盐水，持续6天半。使用热板试验分析动物的吗啡剂量反应，并使用rtPCR评估与一氧化氮代谢相关的几个基因的表达。此外，测量吗啡暴露对Fos和nNOS的免疫组织化学以及vlPAG处的烟酰胺腺嘌呤二核苷酸磷酸黄递酶（NADPH-d）反应的影响。在这两个年龄组中，急性吗啡激活了vlPAG中的Fos，并且这种作用被慢性吗啡减弱，特别是在vlPAG中的背外侧被盖核（LDTg）的水平。在成年人中，但不是PD 7大鼠，慢性吗啡给药与一氧化氮功能的激活有关。相反，PD 7大鼠基因表达的变化表明可能参与了超氧化物和过氧化物代谢。这些数据表明，有脊髓上的神经可塑性吗啡给药后，早在PD 7。此外，与慢性吗啡暴露相关的氧化应激途径似乎具有年龄特异性。
The development of tolerance to the antinociceptive effects of morphine has been associated with networks within ventrolateral periaqueductal gray (vlPAG) and separately, nitric oxide signaling. Furthermore, it is known that the mechanisms that underlie tolerance differ with age. In this study, we used a rat model of antinociceptive tolerance to morphine at two ages, postnatal day (PD) 7 and adult, to determine if changes in the vlPAG related to nitric oxide signaling produced by chronic morphine exposure were age-dependent. Three pharmacological groups were analyzed: control, acute morphine, and chronic morphine group. Either morphine (10 mg/kg) or equal volume of normal saline was given subcutaneously twice daily for 6 ½ days. Animals were analyzed for morphine dose-response using Hot Plate test, and for the expression of several genes associated with nitric oxide metabolism was evaluated using rtPCR. In addition, the effect of morphine exposure on immunohistochemistry for Fos, and nNOS as well as nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reaction at the vlPAG were measured. In both age groups acute morphine activated Fos in the vlPAG, and this effect was attenuated by chronic morphine, specifically in the vlPAG at the level of the laterodorsal tegmental nucleus (LDTg). In adults, but not PD7 rats, chronic morphine administration was associated with activation of nitric oxide function. In contrast, changes in the gene expression of PD7 rats suggested superoxide and peroxide metabolisms may be engaged. These data indicate that there is supraspinal neuroplasticity following morphine administration as early as PD7. Furthermore, oxidative stress pathways associated with chronic morphine exposure appear age-specific.
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影响因子：
4.8
作者：
Ambasta, RK;Kumar, P;Brandes, RP
通讯作者：
Brandes, RP
影响因子：
8.8
作者：
Fonsmark, L;Rasmussen, YH;Carl, P
通讯作者：
Carl, P
DOI：
10.1016/s0006-291x(88)80306-1
发表时间：
1988-12-15
影响因子：
3.1
作者：
CHANG, SL;SQUINTO, SP;HARLAN, RE
通讯作者：
HARLAN, RE
影响因子：
5.8
作者：
Heinzen, EL;Pollack, GM
通讯作者：
Pollack, GM
DOI：
10.1073/pnas.88.7.2811
发表时间：
1991-04-01
影响因子：
11.1
作者：
HOPE, BT;MICHAEL, GJ;VINCENT, SR
通讯作者：
VINCENT, SR