25INBOMe ("25-I", "N-Bomb"), one of new psychoactive substances (NPSs), is being abused for recreational purpose. However, the liability for abuse or dependence has not been systematically studied yet. The objective of the present study was to evaluate rewarding and reinforcing effects of 25INBOMe using conditioned place preference (CPP) and self-administration (SA) paradigms. In addition, ultrasonic vocalizations (USVs) were measured to investigate relationships between USVs and emotional state regarding dependence on psychoactive substances. To understand molecular mechanism involved in its action, dopamine (DA) level changes were analyzed using synaptosomes extracted from the striatal region of the brain. Expression level changes of SGK1 (serum/glucocorticoid regulated kinase 1) and PER2 (period circadian protein homolog 2), two putative biomarkers for drug dependence, were also analyzed. Results showed that 25INBOMe increased both CPP (0.3 mg/kg) and SA (0.03 mg/kg/infusion) and produced higher frequencies in USVs analysis. It also increased DA levels in the striatal region and changed expression levels of SGK1 and PER2. Results of the present study suggest that 25INBOMe might produce rewarding and reinforcing effects, indicating its dependence liability. In addition, frequencies of USV might be associated with emotional state of mice induced by psychoactive substances regarding substance dependence. This is the first systemic preclinical report on the dependence liability of 25INBOMe and the first attempt to introduce a possible relationship between USVs and emotional state of mice regarding substance dependency. Further studies are needed to clarify the mechanism involved in 25INBOMe dependency and determine the usefulness of USV measurement as a method for evaluating dependence liability.

中文翻译：

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2-（4-碘-2,5-二甲氧基苯基）N-（2-甲氧基苄基）乙胺（25INBOMe）的滥用潜能; 体内和离体方法。

25INBOMe（“ 25-I”，“ N-炸弹”）是一种新型精神活性物质（NPS），正被用于娱乐目的。但是，滥用或依赖的责任尚未得到系统的研究。本研究的目的是使用条件性位置偏爱（CPP）和自我管理（SA）范式评估25INBOMe的奖励和增强作用。另外，测量了超声发声（USV），以研究USV与情绪状态之间关于对精神活性物质的依赖性之间的关系。为了了解参与其作用的分子机制，使用了从大脑纹状体区域提取的突触小体来分析多巴胺（DA）的水平变化。SGK1（血清/糖皮质激素调节的激酶1）和PER2（周期的昼夜节律蛋白同系物2）的表达水平变化，还分析了两个推定的药物依赖性生物标志物。结果表明25INBOMe可以增加CPP（0.3 mg / kg）和SA（0.03 mg / kg /输液）并在USVs分析中产生更高的频率。它还增加了纹状体区域的DA水平，并改变了SGK1和PER2的表达水平。本研究结果表明25INBOMe可能产生奖励和增强作用，表明其依赖性责任。此外，USV的频率可能与精神活性物质诱发的依赖物质依赖的小鼠的情绪状态有关。这是有关25INBOMe依赖责任的第一份系统性临床前报告，也是首次尝试在USV与小鼠关于物质依赖的情绪状态之间建立可能的关系。