期刊
ADDICTION BIOLOGY
卷 26, 期 1, 页码 -出版社
WILEY
DOI: 10.1111/adb.12884
关键词
Dual-specificity phosphatase 15; memory; Morphine
资金
- Social Development Science and Technology Research Project of Shaanxi Province [2017SF-244]
- National Natural Science Foundation of China [81571858]
- National Key Research and Development Program [2018YFA0107303]
The study identified DUSP15 as a key regulator in preventing the expression of drug-paired contextual memory and promoting the extinction of existing addiction memories, offering a novel therapeutic target for drug addiction treatment.
Drug relapse among addicts often occurs due to the learned association between drug-paired cues and the rewarding effects of these drugs, such as morphine. Contextual memory associated with morphine has a central role in maintenance and relapse. We showed that morphine-conditioned place preference (CPP) activates extracellular-regulated protein kinase (ERK) in the nucleus accumbens (NAc). The main enzymes that mediate ERK dephosphorylation are members of the dual-specificity phosphatase (DUSP) superfamily. It is unclear which members regulate the morphine CPP-induced activation of ERK. After screening, DUSP15 was found to be decreased during both morphine CPP expression and the reinstatement period. Intra-NAc infusions of AAV-DUSP15 (overexpression) not only prevented the expression of morphine-induced CPP but also facilitated extinction, inhibited reinstatement, and abolished ERK activation. However, after repeated morphine exposure and withdrawal in mice, there was no change in the expression of p-ERK and DUSP15, and the overexpression of DUSP15 in the NAc did not improve the impaired spatial memory or anxiety-like behaviour induced by morphine. Together, these findings indicate that DUSP15 not only prevents the expression of drug-paired contextual memory but also promotes the extinction of existing addiction memories, thus providing a novel therapeutic target for the treatment of drug addiction.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据