Activation of AMPK-dependent autophagy in the nucleus accumbens opposes cocaine-induced behaviors of mice
Activation of AMPK-dependent autophagy in the nucleus accumbens opposes cocaine-induced behaviors of mice
复制标题
伏隔核中 AMPK 依赖性自噬的激活可对抗可卡因诱导的小鼠行为
DOI：
10.1111/adb.12736
复制
发表时间：
2020-03-01
影响因子：
3.4
通讯作者：
Wang, Fang
中科院分区：
文献类型：
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作者：
Lu, Hai-Feng;Xiao, Wen;Wang, Fang
可卡因是一种强烈的中枢神经系统兴奋剂，可诱发药物成瘾。先前的研究已经报道可卡因诱导的自噬参与神经炎症和细胞死亡。然而，自噬在可卡因的精神敏感性中的作用尚未被探索。本文报道了D-1受体-CaMKII-AMPK-FoxO 3a信号通路参与可卡因诱导的大鼠海马神经核（NAc）细胞自噬过程。此外，我们发现NAc中ATG 5基因的敲低增强了对可卡因的行为反应，并且用雷帕霉素诱导NAc中的自噬减弱了可卡因诱导的行为反应，这与NAc神经元树突棘密度的改变一致。这些结果表明，可卡因暴露会诱导自噬，这是雄性小鼠对可卡因行为反应的保护机制。
Cocaine is a strong central nervous system stimulant, which can induce drug addiction. Previous studies have reported that cocaine-induced autophagy is involved in neuroinflammation and cell death. However, the role of autophagy in psychomotor sensitivity to cocaine has not been explored. Here, we reported that D-1 receptor -CaMKII-AMPK-FoxO3a signaling pathway was involved in acute cocaine application-induced autophagy in the nucleus accumbens (NAc) both in vitro and in vivo. Furthermore, we found that knockdown of the ATG5 gene in the NAc augmented behavioral response to cocaine, and induction of autophagy in the NAc with rapamycin attenuated cocaine-induced behavioral response, which was coincident with the alterations of dendritic spine density in neurons of NAc. These results suggest that cocaine exposure leads to the induction of autophagy, which is a protective mechanism against behavioral response to cocaine of male mice.