Effects of aquaporin 4 deficiency on the expression of spinal PKCα, PKCγ and c-Fos in naloxone-precipitated morphine withdrawal mice / 生理学报

ABSTRACT

The previous study indicated that aquaporin 4 (AQP4) deficiency attenuated opioid physical dependence. However, the underlying mechanism remains unknown. In the present study, the effects of AQP4 deficiency on the expression of three factors, protein kinase C (PKC) α, PKCγ and c-Fos in the spinal cord, which are known to be concerned with spinal neuronal sensitization and opiate dependence, were investigated in AQP4 knockout mice using Western blotting analysis. It was observed that AQP4 deficiency reduced the score of naloxone-precipitated abstinent jumping after repeated morphine administration compared with wild-type (P < 0.001). Meanwhile, the protein levels of PKCα and c-Fos in the spinal cord of AQP4 knockout mice were significantly higher than those in the wild-type mice; while the expression of PKCγ was decreased remarkably by AQP4 knockout during the withdrawal (P < 0.01). These data suggest that AQP4 deficiency-attenuated morphine withdrawal responses may be partially attributed to the changes in the spinal expression of PKCα, PKCγ or c-Fos.