MDMA abuse continues being a serious problem in our society. Environmental factors, such as stress, increase the vulnerability of individuals to develop drug abuse and we have observed that exposure to social defeat (SD) stress alters the sensitivity of mice to the rewarding effects of MDMA in the conditioned place preference (CPP) paradigm. In the present study, we evaluated the role of the nitric oxide (NO) pathway in the effects of SD on the rewarding properties of MDMA. Three groups of mice were treated with an inhibitor of NO synthesis, 7-nitroindazole (0, 7.25 and 12.5 mg/kg), before each exposure to SD and place conditioning with MDMA (1.25 mg/kg) on PND 54, 56, 58, and 60. One control group was not exposed to SD before place conditioning. In addition, we studied the effects of SD on the levels of nitrites in the striatum, hippocampus and frontal cortex. Our results showed that the low dose of 7-nitroindazole blocked the effects of SD on the rewarding properties of MDMA. Moreover, SD exposure increased the nitrites in the prefrontal cortex and hippocampus. These results demonstrated the role of NO signalling in the effects of SD stress in mice and suggested that the inhibition of NO synthesis may confer resilience to the effects of social stress on the rewarding properties of MDMA. The manipulation of the NO signalling pathway could be a useful target for the treatment of MDMA-dependent subjects who experienced high levels of stress.

中文翻译：

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一氧化氮信号传导的阻滞增强了抵御社交失败压力对小鼠MDMA条件性奖励特性的影响的适应力。

MDMA滥用仍然是我们社会中的一个严重问题。环境因素（例如压力）增加了个体发展药物滥用的脆弱性，并且我们已经观察到，遭受社会失败（SD）压力的暴露会改变小鼠对条件位置偏好（CPP）范式中MDMA奖励作用的敏感性。在本研究中，我们评估了一氧化氮（NO）途径在SD对MDMA奖励特性的影响中的作用。在每次暴露于SD之前，将三组小鼠用一氧化氮合成抑制剂7-硝基吲唑（0、7.25和12.5 mg / kg）处理，并在PND 54,56,58上用MDMA（1.25 mg / kg）进行调理。 60。一个对照组在进行场所调理前未暴露于SD。此外，我们研究了SD对纹状体中亚硝酸盐含量的影响，海马和额叶皮层。我们的结果表明，低剂量的7-硝基吲唑阻断了SD对MDMA奖励特性的影响。此外，SD暴露会增加额叶前额叶皮层和海马中的亚硝酸盐。这些结果证明了NO信号在小鼠SD应激中的作用，并表明NO合成的抑制可能赋予社会应激对MDMA奖励特性的影响的适应力。NO信号通路的操纵可能是治疗遭受高水平压力的依赖MDMA的受试者的有用靶标。这些结果证明了NO信号在小鼠SD应激中的作用，并表明NO合成的抑制可能赋予社会应激对MDMA奖励特性的影响的适应力。NO信号通路的操纵可能是治疗遭受高水平压力的依赖MDMA的受试者的有用靶标。这些结果证明了NO信号在小鼠SD应激中的作用，并表明NO合成的抑制可能赋予社会应激对MDMA奖励特性的影响的适应力。NO信号通路的操纵可能是治疗遭受高水平压力的依赖MDMA的受试者的有用靶标。