吗啡戒断性焦虑大鼠VTA和NAc脑区/核团CaMKⅡ含量与磷酸化水平改变

The variable contents and phosphorylation levels of CaMKⅡ in ventral tegmental area and nucleus accumbens in anxious rats suffered from morphine withdrawal

目的:研究阿片类药物依赖戒断后焦虑产生的分子机制。方法:选用健康雄性SD大鼠48只,随机分为生理盐水对照组、模型组和丁螺环酮治疗组。采用剂量递增法皮下注射吗啡10d,自然戒断,并在自然戒断的1～3d给予丁螺环酮15mg/kg灌胃治疗(2次/d),于末次吗啡注射后72h,高架十字迷宫检测大鼠焦虑行为后,用Western Blot法检测各组大鼠奖赏系统中脑腹侧被盖区(VTA)和伏核(NAc)神经细胞钙/钙调素依赖性蛋白激酶Ⅱ(CaMKII)的含量和磷酸化水平。结果:与生理盐水对照组比较,模型组大鼠CaMKⅡ蛋白含量和β亚基磷酸化水平均显著升高(P<0.01);与丁螺环酮组比较,模型组CaMKII蛋白的含量与β亚基的磷酸化水平同样显著增高(P<0.01)。结论:奖赏系统VTA和NAc神经细胞CaMKⅡ含量、CaMKIIβ亚基磷酸化水平的增高可能是吗啡依赖戒断焦虑行为产生的分子机制之一。

Objective：To explore the molecular mechanism of anxiety-like behavioral rats subjected to morphine withdrawal.Methods：48 SD rats were divided into model group,buspirone group and normal sodium group.Gradual increasing dosage of morphine（i.p.）was applied to SD rats for 10 d.Spontaneous withdrawal performed,anxious rats were controlled by 15 mg/kg buspirone（twice per day,i.g.）for 1-3 d.Anxiety-like behavior was validated by the elevated plus maze in rats suffered from 72 h withdrawal.The variable contents and phosphorylation levels of calmodlin-dependent protein kinase Ⅱ（CaMKⅡ）in the ventral tegmental area（VTA）and the nucleus accumbens（NAc）were detected by Western Blot in morphine withdrawal rats.Results：As results presented in the present study,higher content and phosphorylase levels of β-subunit of CaMKⅡwere observed in morphine-withdrawal rats than that of control group（P0.01）.As compared with the group treated with buspirone,higher content and phosphorylase levels of β-subunit of CaMKⅡ also observed in anxious rats（P0.01）.Conclusion：The results suggest that higher content and phosphorylase level of β-subunit of CaMK Ⅱ could be contributed to the developmental symptom in anxiety-like behavioral rats subjected to morphine withdrawal.