慢性吗啡依赖大鼠脑内G_(i2)蛋白的改变

Alterations of G_(i2) proteins in brain regions of morphine tolerant and dependent rats

目的研究慢性吗啡依赖大鼠腹侧背盖区(Ventraltegmentalarea,VTA)、伏隔核(Nucleusaccumbens,NAc)、前额皮质(Prefrontalcortex,PC)、海马(Hippocampus)及去甲肾上腺能神经中枢蓝斑(Locuscoeruleus,LC)五个脑区Gi2蛋白的改变,探讨慢性吗啡依赖的可能机制。方法18只SD大鼠随机分为三组:慢性吗啡依赖组、戒断组和空白对照组。慢性吗啡依赖组和戒断组腹腔注射吗啡,建立吗啡成瘾模型,戒断组腹腔注射纳络酮(5mg/kg)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。结果慢性吗啡成瘾组和戒断组与空白对照组相比,NAc区Gi2蛋白水平明显降低(P<0.01),LC区Gi2蛋白水平却明显升高(P<0.01),其它脑区未发现明显变化。结论慢性吗啡成瘾可引起大鼠脑内Gi2蛋白水平发生改变,但各脑区Gi2蛋白水平的改变并不相同。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 chronic morphine addiction rats with the technique of immunohistochemistry in five brain regions （ventral tegmental area, nucleus accumbens, prefrontal cortex, hippocampus and locus coeruleus）.Methods Eighteen adult male SpragueDawley rats were divided randomly into three groups （n=6）： chronic morphine dependent group,chronic abstinent group and chronic control group.Chronic 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 sydromes with naloxone 5mg/kg for 30min.The rats in control group were injected with Saline.All rats were sacrificed by decapitation.The coronal sections of discrete brain regions （ventral tegmental area,nucleus accumbens,prefrontal cortex,locus coeruleus, hippocampus）were cut.The relative concentrations of Gi2 protein were detected by the technique of immunohistochemistry.Results The Gi2 protein didn＇t significantly change in others brain regions（P〉0.05）; in chronic morphine dependent group and chronic abstinent group Gi2 protein were significantly more decrease in nucleus accumbens （P〈0.01）and significantly more increase in locus coeruleus（P〈0.05） than the chronic control group. Compared with the chronic control group,other brain regions didn＇t find the changes（P〉0.05）.Conclusion The 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 oipioid tolerance and dependence.