Heroin-Induced Autophage in the Nucleus Accumbens Is Alleviated by SIRT1 Inhibition

Objective: To investigate the effects of regulating SIRT1 on neuronal autophagy in the nucleus accumbens(NAc) of heroin-addicted mice.Methods: Wild-type C57BL/6J,and sirt1loxp/loxp;D1 Cre(+) knockout mice were constructed using sirt1loxp/loxp.The mouse crosses were divided into saline control and heroin-addicted groups.The heroin-addicted mice model was established by excess intraperitoneal injection of heroin fluid. The withdrawal response was then observed using behavioral methods. Conditioned place preference behavior and excitability of the mice were observed in the open field, while autophagosome structure was detected using transmission electron microscopy. The expression of autophagy-related proteins was analyzed using immunofluorescence.The expression of SIRT1 and autophagy-related proteins and genes, such as LC3II(LC3II/LC3I), ATG5, and ATG7, was detected in NAc of each group using western blot and quantitative real-time PCR.Results: Western blot revealed that compared with the normal saline control group, the expression of SIRT1 protein was in the NAc of heroin-addicted mice.TEM revealed that the NAc of the heroin-addicted group had more autophagosomes than the control group.The expression of autophagy-related genes and proteins,such as LC3II,ATG5,and ATG7,was significantly higher in each heroin-addicted group than in the saline control group.However,autophagy-related genes and proteins,such as LC3II,ATG5,and ATG7,were underexpressed after sirt1 knockout on D1 neurons in the heroin-addicted group.Nonetheless, their expression was still higher in the heroin-addicted group than in the saline control group.Conclusion: sirt1 gene knockout on D1 neurons reduces intra-neuronal autophagy and protects neurons under heroin addiction.