Background The proliferation of Novel Psychoactive Substances (NPS) in the drug market raises concerns about uncertainty on their pharmacological profile and the health hazard linked to their use. Within the category of synthetic stimulant NPS, the phenethylamine 2-Cl-4,5-methylenedioxymethamphetamine (2-Cl-4,5-MDMA) has been linked to severe intoxication requiring hospitalization. Thereby, the characterization of its pharmacological profile is urgently warranted. Methods By in vivo brain microdialysis in adolescent and adult male rats we investigated the effects of 2-Cl-4,5-MDMA on dopamine (DA) and serotonin (5-HT) neurotransmission in two brain areas critical for the motivational and reinforcing properties of drugs, the nucleus accumbens (NAc) shell and the medial prefrontal cortex (mPFC). Moreover, we evaluated the locomotor and stereotyped activity induced by 2-Cl-4,5-MDMA, and the emission of 50-kHz ultrasonic vocalizations (USVs) to characterize its affective properties. Results 2-Cl-4,5-MDMA increased dialysate DA and 5-HT in a dose-, brain area-, and age-dependent manner. Notably, 2-Cl-4,5-MDMA more markedly increased dialysate DA in the NAc shell and mPFC of adult than adolescent rats, while the opposite was observed on dialysate 5-HT in the NAc shell, with adolescent rats being more responsive. Furthermore, 2-Cl-4,5-MDMA stimulated locomotion and stereotyped activity in both adolescent and adult rats, although to a greater extent in adolescents. Finally, 2-Cl-4,5-MDMA did not stimulate 50-kHz USV emissions. Conclusions This is the first pharmacological characterization of 2-Cl-4,5-MDMA demonstrating that its neurochemical and behavioral effects may differ between adolescence and adulthood. These preclinical data could help understanding the central effects of 2-Cl-4,5-MDMA, by increasing awareness on possible health damage in users.

中文翻译：

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苯乙胺 2-Cl-4,5-Mdma 对青春期和成年雄性大鼠的神经化学和行为影响的表征

背景 新型精神活性物质（NPS）在药品市场上的激增引起了人们对其药理特征的不确定性以及与其使用相关的健康危害的担忧。在合成兴奋剂 NPS 类别中，苯乙胺 2-Cl-4,5-亚甲基二氧基甲基苯丙胺 (2-Cl-4,5-MDMA) 与需要住院治疗的严重中毒有关。因此，迫切需要对其药理学特征进行表征。方法 通过对青春期和成年雄性大鼠进行体内脑微透析，我们研究了 2-Cl-4,5-MDMA 对两个大脑区域中多巴胺 (DA) 和血清素 (5-HT) 神经传递的影响，这两个区域对激励和强化特性至关重要药物、伏隔核 (NAc) 壳和内侧前额皮质 (mPFC)。此外，我们评估了 2-Cl-4,5-MDMA 诱导的运动和刻板活动，以及 50 kHz 超声波发声 (USV) 的发射，以表征其情感特性。结果 2-Cl-4,5-MDMA 以剂量、脑区域和年龄依赖性方式增加透析液 DA 和 5-HT。值得注意的是，与青少年大鼠相比，2-Cl-4,5-MDMA 更显着地增加了成年大鼠 NAc 壳和 mPFC 中的透析液 DA，而 NAc 壳中透析液 5-HT 的观察结果相反，其中青少年大鼠的反应更灵敏。此外，2-Cl-4,5-MDMA 刺激青少年和成年大鼠的运动和定型活动，但在青少年中刺激程度更大。最后，2-Cl-4,5-MDMA 不会刺激 50-kHz USV 发射。结论 这是 2-Cl-4,5-MDMA 的第一个药理学特征，表明其神经化学和行为效应在青春期和成年期可能有所不同。这些临床前数据可以通过提高对使用者可能的健康损害的认识来帮助了解 2-Cl-4,5-MDMA 的核心作用。