Uimyung Research Institute for Neuroscience, Sahmyook University, Seoul, Republic of Korea.
Department of Chemistry and Life Science, Sahmyook University, Seoul, Republic of Korea.
J Psychopharmacol. 2020 Sep;34(9):1056-1067. doi: 10.1177/0269881120936458. Epub 2020 Jul 10.
Recently, the recreational use of substituted phenethylamines has grown rapidly. Among these are 2-(3,5-dimethoxy-4-((2-methylallyl)oxy)phenyl)ethanamine (MAL) and 2-(2,5-dimethoxy-4-methylphenyl)-2-methoxyethan-1-amine (BOD). However, studies characterizing their abuse potential are still lacking.
The purpose of this study was to investigate the abuse potential of MAL and BOD.
The psychostimulant, reinforcing, and rewarding properties of MAL and BOD were analyzed using locomotor sensitization, self-administration, and conditioned place preference tests. Dopamine antagonists (i.e. SCH23390, haloperidol) were administered during conditioned place preference to evaluate the involvement of the mesolimbic dopamine system. Furthermore, dopamine-related protein expression in the nucleus accumbens and the ventral tegmental area was measured along with dopamine concentrations in the nucleus accumbens. Electroencephalography was conducted to determine effects of MAL and BOD on brain wave activity.
MAL induced psychostimulant effects and sensitization, while BOD induced locomotor depression in mice. Only MAL was self-administered by rats. Both drugs induced conditioned place preference in mice at different doses; dopamine receptor antagonists blocked MAL- and BOD-induced conditioned place preference. Both the compounds altered the expression of dopamine receptor D and D proteins in the nucleus accumbens and tyrosine hydroxylase (TH) and dopamine transporter in the ventral tegmental area, enhanced dopamine levels in the nucleus accumbens, and increased delta and gamma wave activities in the brain.
MAL may induce abuse potential via the mesolimbic dopaminergic system and possibly accompanied by alterations in brain wave activity. Moreover, the lack of rewarding and reinforcing effects in BOD suggest that this drug may have little to no capability to engender compulsive behavior, though having found to induce alterations in dopaminergic system and brain wave activities.
最近，娱乐性使用取代苯乙胺的现象迅速增加。其中包括 2-(3,5-二甲氧基-4-((2-甲基烯丙基)氧基)苯基)乙胺 (MAL) 和 2-(2,5-二甲氧基-4-甲基苯基)-2-甲氧基乙-1-胺 (BOD)。然而，描述它们的滥用潜力的研究仍然缺乏。
本研究旨在探讨 MAL 和 BOD 的滥用潜力。
使用运动敏化、自我给药和条件性位置偏好测试来分析 MAL 和 BOD 的精神兴奋剂、强化和奖赏特性。在条件性位置偏好期间给予多巴胺拮抗剂（即 SCH23390、氟哌啶醇），以评估中脑边缘多巴胺系统的参与。此外，还测量了伏隔核和腹侧被盖区的多巴胺相关蛋白表达以及伏隔核中的多巴胺浓度。进行脑电图以确定 MAL 和 BOD 对脑电波活动的影响。
MAL 诱导精神兴奋剂作用和敏化，而 BOD 诱导小鼠运动抑制。只有 MAL 被大鼠自我给药。两种药物以不同剂量诱导小鼠产生条件性位置偏好；多巴胺受体拮抗剂阻断 MAL 和 BOD 诱导的条件性位置偏好。两种化合物均改变了伏隔核中多巴胺受体 D 和 D 蛋白的表达以及腹侧被盖区中的酪氨酸羟化酶 (TH) 和多巴胺转运体，并增强了伏隔核中的多巴胺水平，增加了脑电波中的 delta 和 gamma 波活动。
MAL 可能通过中脑边缘多巴胺能系统诱导滥用潜力，并且可能伴随着脑电波活动的改变。此外，BOD 缺乏奖赏和强化作用表明，这种药物可能几乎没有能力引起强迫行为，尽管已经发现它会引起多巴胺能系统和脑电波活动的改变。
