Effects of over-expression of u-opioid receptor on methamphetamine-sensitization

我们首次证明注射AAV-MOR可增强脑内MOR免疫反应性。通过细胞培养，我们发现AAV-MOR能增加293细胞的MOR结合率和MOR免疫反应性。这些数据表明，AAV-MOR治疗在体内和体外都能增强MOR的表达。 将AAV-MOR或AAV-GFP注射到成年C57/BL6小鼠的伏隔核(NAC)或腹侧被盖区(VTA)。病毒感染两周后，动物连续5天注射甲基苯丙胺或生理盐水。反复给予甲基苯丙胺可逐渐增加小鼠的运动活动；这种敏化反应可被NAC AAV-MOR预处理减弱。相反，向VTA注射AAV-MOR可增强甲基苯丙胺的敏化作用。 AAV-MOR显著增加VTA感染后VTA内DA的水平，但降低注射NAC后NAc内DOPAC/DA的转换率。我们的数据表明，在NAC和VTA中，MOR的过度表达对甲基苯丙胺的敏化有不同的调制作用。

We first demonstrated that injection of AAV-MOR increased MOR immunoreactivity in brain. Using cell culture, we found that AAV-MOR transfection can increase MOR binding and MOR immunoreactivity in 293 cells. These data suggest that treatment with AAV-MOR enhances MOR expression in vivo and in vitro. AAV-MOR or AAV-GFP was then injected into the nucleus Accumbens (NAc) or ventral tegmental area (VTA) of adult C57/BL6 mice. Two weeks after viral infection, animals received methamphetamine or saline for 5 consecutive days. Repeated administration of methamphetamine progressively increased locomotor activity; this sensitization reaction was attenuated by NAc AAV-MOR pretreatment. In contrast, administration of AAV-MOR to VTA enhanced methamphetamine sensitization. AAV-MOR significantly enhanced DA levels in VTA after VTA infection but reduced DOPAC/DA turnover in the NAc after NAc injection. Our data suggest a differential modulation of methamphetamine sensitization by overexpression of MOR in NAc and VTA.