Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System,ACS Chemical Neuroscience

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Designer Drug, 25D-NBOMe, Has Reinforcing and Rewarding Effects through Change of a Dopaminergic Neurochemical System
ACS Chemical Neuroscience ( IF 4.1 ) Pub Date : 2023-07-18 , DOI: 10.1021/acschemneuro.3c00196
Jae-Gyeong Lee ₁ , Kwang-Hyun Hur ₁ , Su-Bin Hwang ₁ , Sooyeun Lee ₂ , Seok-Yong Lee ₁ , Choon-Gon Jang ₁

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2-(2,5-Dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)_ethanamine (25D-NBOMe), an analogue of the 2C family, is a newly synthesized psychoactive substance. It acts as an agonist at the 5-HT_2A receptor and has a similar mechanism to that of NBOMe compounds. However, the pharmacological mechanism for its rewarding and reinforcing effects has not been revealed. In the present study, intravenous self-administration (IVSA) test and conditioned place preference (CPP) test were performed to investigate whether 25D-NBOMe has abuse potential. We also evaluated the effects of 25D-NBOMe on neurochemical changes using western blot analysis and microdialysis. The IVSA test revealed increased self-administration in 25D-NBOMe (0.03 mg/kg)-treated rats. In addition, the CPP test revealed rewarding effects in 25D-NBOMe (1 mg/kg)-treated mice. In the neurochemical studies, 25D-NBOMe treatment affected the expression of dopamine (DA) receptor D1 (DRD1), DA receptor D2 (DRD2), tyrosine hydroxylase, DA transporter (DAT), and phospho-DAT (p-DAT) in the nucleus accumbens (NAc). In addition, microdialysis revealed that treatment with progressively increasing doses (1, 3, and 10 mg/kg) of 25D-NBOMe increased the extracellular levels of DA, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the rat NAc. Taken together, our results show the abuse potential and neurochemical changes related to addictive behavior after administration of 25D-NBOMe.

中文翻译：

设计药物 25D-NBOMe 通过改变多巴胺能神经化学系统具有强化和奖励作用

2-(2,5-二甲氧基-4-甲基苯基)-N- ( 2-甲氧基苄基)_乙胺(25D-NBOMe)是2C家族的类似物，是一种新合成的精神活性物质。它作为 5-HT _2A受体的激动剂，具有与 NBOMe 化合物相似的机制。然而，其奖励和增强作用的药理学机制尚未揭示。在本研究中，进行了静脉自我给药（IVSA）试验和条件性位置偏好（CPP）试验来调查25D-NBOMe是否具有滥用潜力。我们还使用蛋白质印迹分析和微透析评估了 25D-NBOMe 对神经化学变化的影响。IVSA 测试显示，25D-NBOMe (0.03 mg/kg) 治疗的大鼠的自我给药量增加。此外，CPP 测试还揭示了 25D-NBOMe (1 mg/kg) 治疗小鼠的奖励效应。在神经化学研究中，25D-NBOMe 治疗影响多巴胺 (DA) 受体 D1 (DRD1)、DA 受体 D2 (DRD2)、酪氨酸羟化酶、DA 转运蛋白 (DAT) 和磷酸-DAT (p -DAT) 的表达。伏隔核（NAc）。此外，微透析显示，逐渐增加剂量（1、3 和 10 mg/kg）的 25D-NBOMe 治疗可增加大鼠 NAc 中 DA、3,4-二羟基苯乙酸和高香草酸的细胞外水平。综上所述，我们的结果显示了 25D-NBOMe 给药后与成瘾行为相关的滥用潜力和神经化学变化。

更新日期：2023-07-18

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