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bioRxiv · 10.1101/743062

Sirt3 mediated by lentiviral vectors in the periaqueductal gray suppresses morphine withdrawal in rats: A preliminary study

Liu, S.·Yi, H.·GU, J.·Ikegami, D.·Hayashi, K.·Hao, S.
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Abstract

Opioid use disorder (OUD) is a significant clinical and social problem, inducing dependence/addiction and over-dose death. Opioid dependence/withdrawal contributes to the addiction vulnerability. Limited understanding of the exact mechanisms of morphine withdrawal leads to failure to adequately manage opioid withdrawal symptoms. Determining new molecular mechanisms of morphine withdrawal (MW) may allow development of novel therapeutic strategies for treating this disorder. Chronic morphine with naloxone precipitation induces MW behavioral response. Sirt3 (one member of sirtuins family) as a mitochondrial fidelity, plays an important role in mitochondrial homeostasis through the direct regulation of mitochondrial energy metabolism, ATP synthesis, detoxification of mitochondrial ROS, etc. In the pilot study, we found that (1) cultured neurons infected with lentiviral vector expressing Sirt3 induced over-expression of Sirt3, (2) microinjection of LV-Sirt3 into the vlPAG increased Sirt3 protein expression in rats, (3) MW lowered the expression of Sirt3 in the vlPAG, and (4) microinjection of LV-Sirt3 into the vlPAG decreased the MW behavioral response. Current preliminary study demonstrates that complement of Sirt3 in the PAG suppressed MW, providing a novel therapeutic approach to morphine physical withdrawal symptoms. The exact up-and/or down-stream factors of Sirt3 in the model are under the investigation.

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Liu, S., Yi, H., GU, J., Ikegami, D., Hayashi, K., Hao, S.. 2019-08-22. Sirt3 mediated by lentiviral vectors in the periaqueductal gray suppresses morphine withdrawal in rats: A preliminary study. https://doi.org/10.1101/743062

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