急性吗啡依赖大鼠脑内G_(i2)蛋白的表达

Changes of expression of G_(i2) protein in rat brain of acute morphine addiction

目的研究急性吗啡成瘾后大鼠腹侧背盖区(Ventral tegmental area,VTA)、伏隔核(Nucleus accumbens,NAc)、前额皮质(Prefrontal cortex,PC)、海马(Hippocampus)及去甲肾上腺能神经中枢蓝斑(Locus coeruleus,LC)五个脑区Gi2蛋白的改变,探讨急性吗啡成瘾的可能机制。方法18只SD大鼠随机分为三组,每组6只,分别是急性吗啡成瘾组、急性吗啡戒断组、空白对照组。吗啡成瘾组和戒断组腹腔注射吗啡,直到吗啡成瘾模型建立。戒断组腹腔注射纳络酮5mg/kg,作用30min后断头处死各组大鼠。取出脑组织,进行冰冻切片。用免疫组化技术检测NAc、PC、LC、VTA和Hippocampus五个脑区相对Gi2蛋白水平。结果急性吗啡成瘾组和急性戒断组与空白对照组相比,NAc区Gi2蛋白水平有明显降低(P<0.01),其它脑区则未发现明显的改变。结论急性吗啡成瘾可引起大鼠脑内Gi2蛋白水平发生改变,NAc区Gi2蛋白水平有明显降低,其它脑区则未发现明显的改变。Gi2蛋白水平的改变可能是吗啡耐受和依赖潜在的分子机制。

Objective To investigate the changes of Gi2 proteins of acute morphine addiction rats with the technique of immunohistochemistry in five brain regions： Ventral tegmental area （VTA）,nucleus accumbens （NAt）, prefrontal cortex （PC）, hippocampus and locus coeruleus （LC）.Methods Eighteen adult male Sprague-Dawley rats were divided randomly into three groups （n=6）：acute morphine- dependent group,acute abstinent group,controlled group. Dependent groups and abstinent group were administered with morphine by intraperitoneal injection till morphine- dependent models were founded.The rats in abstinent groups were induced withdrawal syndromes with naloxone 5mg/kg for 30min.The rats in controlled group were injected with Saline.All the rats were sacrificed by decapitation.The corona/led sections of discreted brain regions （TA,NAc,PC,LC, and Hippocampus）were cut.The relative concentrations of Go protein were detected by the immunohistochemistry technique.Results Gi2 protein levels of acute morphine dependent group and acute abstinent group in NAc were significantly more decreased than that of the acute controlled group （P〈0.01）. The Gi2 protein didn＇t significantly change in others brain regions （P〉0.05）.Conclusion The acute morphine-induced differential changes in Gi2 protein levels may reflect changes in gene expression and the result in changes of Gi2 protein may affect signal transduction pathways in morphine dependent animals.Maybe that is the molecular mechanism of opioid tolerance and dependence.