Abstract:
This study investigates the impact of SCs consumption by assessing the effects of three novel synthetic cannabinoids (SCs); MDMB-CHMINACA, 5F-ADB-PINACA, and APICA post-drug treatment. SCs are known for their rapid onset (<1 min) and prolonged duration (≥5 h). Therefore, this research aimed to assess behavioral responses and their correlation with endocannabinoids (ECs) accumulation in the hippocampus, and EC\'s metabolic enzymes alteration at different timeframes (1-3-5-h) following drug administration. Different extents of locomotive disruption and sustained anxiety-like symptoms were observed throughout all-encompassing timeframes of drug administration. Notably, MDMB-CHMINACA induced significant memory impairment at 1 and 3 h. Elevated levels of anandamide (AEA) and 2-arachidonoyl glycerol (2-AG) were detected 1 h post-MDMB-CHMINACA and 5F-ADB-PINACA administration. Reduced mRNA expression levels of fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL) (AEA and 2-AG degrading enzymes, respectively), and brain-derived neurotrophic factor (BDNF) occurred at 1 h, with FAAH levels remaining reduced at 3 h. These findings suggest a connection between increased EC content and decreased BDNF expression following SC exposure. Cognitive disruption, particularly motor coordination decline and progressive loss manifested in a time-dependent manner across all the analyzed SCs. Our study highlights the importance of adopting a temporal framework when assessing the effects of SCs.
摘要:
本研究通过评估三种新型合成大麻素(SC)的影响来调查SC消耗的影响;MDMB-CHMINACA,5F-ADB-PINACA,和APICA药物治疗后。SCs以其快速起效(<1分钟)和延长的持续时间(≥5小时)而闻名。因此,这项研究旨在评估行为反应及其与海马中内源性大麻素(ECs)积累的相关性,和EC的代谢酶在不同的时间框架(1-3-5-h)给药后的变化。在整个药物施用的全部时间范围内,观察到不同程度的机车中断和持续的焦虑样症状。值得注意的是,MDMB-CHMINACA在1和3小时时引起明显的记忆障碍。在MDMB-CHMINACA和5F-ADB-PINACA给药后1小时,检测到anandamide(AEA)和2-花生酰甘油(2-AG)的水平升高。脂肪酸酰胺水解酶(FAAH)mRNA表达水平降低,单酰基甘油脂肪酶(MAGL)(AEA和2-AG降解酶,分别),脑源性神经营养因子(BDNF)发生在1小时,FAAH水平在3小时时保持降低。这些发现表明SC暴露后EC含量增加和BDNF表达减少之间存在联系。认知中断,特别是在所有分析的SC中,以时间依赖性方式表现出的运动协调性下降和进行性丧失。我们的研究强调了在评估SC的影响时采用时间框架的重要性。