Dual-specificity phosphatase 15 (DUSP15) in the nucleus accumbens is a novel negative regulator of morphine sensitization / 西安交通大学学报(医学版)

ABSTRACT

【Objective】 To study the role of dual-specificity phosphatase 15 （DUSP15） in mouse nucleus accumbens （NAc） in morphine sensitization. 【Methods】 The distance was recorded by open field test （OFT）， and morphine sensitization behavior was observed by acute morphine administration. The protein expressions of extracellular regulated protein kinases （ERK）， p-ERK and DUSP15 were tested using Western blotting. DUSP15-overexpressed virus （AAV-DUSP15） was injected into mouse NAc by brain stereotactic injection. Immunofluorescence staining confirmed viral expression. Western blotting was used to detect the effect of AAV-DUSP15 on the expressions of DUSP15， ERK and P-ERK. OFT was used to observe morphine sensitization behavior. 【Results】 The sensitization behavior was induced by intraperitoneal injection of 10 mg/kg morphine （continuous injection of 1 dose/day， for 7 doses） and withdrawal of morphine for 1 week. Compared with the saline control group， p-ERK was found to be increased and DUSP15 was found to be decreased. Intra-NAc infusions of AAV-DUSP15 （overexpression） not only inhibited the expression of p-ERK but also prevented morphine sensitization behavior. 【Conclusion】 DUSP15 negatively regulates ERK activation level in mouse NAc. DUSP15 agonist has a potential therapeutic effect on drug addiction.