Characterization of the Neurochemical and Behavioral Effects of the Phenethylamine 2-Cl-4,5-MDMA in Adolescent and Adult Male Rats.

IF 4.5 2区 医学 Q1 CLINICAL NEUROLOGY
Gessica Piras, Cristina Cadoni, Francesca Caria, Nicholas Pintori, Enrica Spano, Maksims Vanejevs, Anastasija Ture, Graziella Tocco, Nicola Simola, Maria Antonietta De Luca
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引用次数: 0

Abstract

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 rewarding 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 the emission of 50-kHz USVs.

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.

表征苯乙胺 2-Cl-4,5-Mdma 对青春期和成年雄性大鼠神经化学和行为的影响
背景:新型精神活性物质(NPS)在毒品市场上的激增引起了人们对其药理特征的不确定性及其使用对健康危害的担忧。在合成兴奋剂类 NPS 中,苯乙胺 2-Cl-4,5-亚甲二氧基甲基苯丙胺(2-Cl-4,5-MDMA)与需要住院治疗的严重中毒有关。因此,迫切需要对其药理特征进行分析:通过对青少年和成年雄性大鼠进行体内脑微量透析,我们研究了 2-Cl-4,5-MDMA 对多巴胺(DA)和血清素(5-HT)神经传递的影响,这两个脑区对药物的动机和强化特性至关重要,它们分别是伏隔核(NAc)外壳和内侧前额叶皮层(mPFC)。此外,我们还评估了2-Cl-4,5-MDMA诱导的运动和刻板活动,以及50千赫兹超声波发声(USVs),以确定其情感特性。值得注意的是,2-Cl-4,5-MDMA 对成年大鼠 NAc 外壳和 mPFC 中透析液 DA 的增加作用比对青少年大鼠更明显,而对 NAc 外壳中透析液 5-HT 的增加作用则与之相反,青少年大鼠的反应更明显。此外,2-Cl-4,5-MDMA 对青春期和成年大鼠的运动和刻板活动都有刺激作用,但对青春期大鼠的作用更大。最后,2-Cl-4,5-MDMA 不会刺激 50 千赫 USV 发射:这是首次对 2-Cl-4,5-MDMA进行药理学特征描述,表明其对神经化学和行为的影响可能在青春期和成年期有所不同。这些临床前数据有助于了解 2-氯-4,5-二甲基亚砜的中枢效应,提高对使用者可能造成的健康损害的认识。
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来源期刊
CiteScore
8.40
自引率
2.10%
发文量
230
审稿时长
4-8 weeks
期刊介绍: The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.
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