Rationale

Mephedrone is a frequently overused drug of abuse that belongs to the group of novel psychoactive substances. Although its mechanism of action, as well as toxic and psychoactive effects, has been widely studied, the role of different factors that could contribute to the increased vulnerability to mephedrone abuse is still poorly understood.

Objectives

The aim of the presented study was to assess the impact of several factors (sex differences, social-conditioning, and chronic mild unpredictable stress — CMUS) on the liability to mephedrone-induced reward in Wistar rats.

Methods

The rewarding effects of mephedrone in male and female rats were assessed using the conditioned place preference (CPP) procedure. Furthermore, the impact of social factor and stress was evaluated in male rats using social-CPP and CMUS-dependent CPP, respectively.

Results

Mephedrone induced classic-CPP in female (10 mg/kg), as well as in male (10 and 20 mg/kg) rats. However, the impact of mephedrone treatment during social-CPP was highly dose-dependent as the rewarding effects of low dose of mephedrone (5 mg/kg; non-active in classic-CPP) were potentiated when administered during social-conditioning. Interestingly, social-conditioning with a higher dose of 20 mg/kg (that induced classic-CPP) was able to reverse these effects. Finally, CMUS potentiated rewarding effects of a low dose of mephedrone (5 mg/kg) and increased the level of corticosterone in rats’ prefrontal cortex and hippocampus.

Conclusions

Altogether, the presented results give new insight into possible factors underlying the vulnerability to mephedrone abuse and can serve as a basis for further studies assessing mechanisms underlying observed effects.

中文翻译：

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甲氧麻黄酮诱发大鼠条件性位置偏好的脆弱因素——性别差异、社会条件和压力的影响

基本原理

甲氧麻黄酮是一种经常滥用的滥用药物，属于新型精神活性物质。尽管其作用机制以及毒性和精神作用已被广泛研究，但可能导致甲氧麻黄酮滥用易感性增加的不同因素的作用仍然知之甚少。

目标

本研究的目的是评估几个因素（性别差异、社会条件和慢性轻度不可预测压力 - CMUS）对 Wistar 大鼠对甲氧麻黄酮诱导的奖励的敏感性的影响。

方法

使用条件性位置偏好 (CPP) 程序评估甲氧麻黄酮对雄性和雌性大鼠的奖励作用。此外，分别使用社会 CPP 和依赖 CMUS 的 CPP 在雄性大鼠中评估社会因素和压力的影响。

结果

Mephedrone 在雌性 (10 mg/kg) 和雄性 (10 和 20 mg/kg) 大鼠中诱导经典 CPP。然而，在社交-CPP 期间，甲氧麻黄酮治疗的影响是高度剂量依赖性的，因为在社交调节期间给予低剂量的甲氧麻黄酮（5 mg/kg；在经典-CPP 中无活性）的奖励作用会增强。有趣的是，使用 20 mg/kg 更高剂量（诱导经典 CPP）的社会调节能够逆转这些影响。最后，CMUS 增强了低剂量甲氧麻黄酮 (5 mg/kg) 的奖励作用，并增加了大鼠前额叶皮层和海马中皮质酮的水平。

结论

总而言之，所呈现的结果对甲氧麻黄酮滥用脆弱性的可能因素提供了新的见解，并可作为进一步研究评估观察到的影响机制的基础。