Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarangro, Nowon-gu, Seoul, 01795, Republic of Korea; Centre for Neuroscience and Regenerative Medicine, Faculty of Science, University of Technology Sydney, New South Wales, 2007, Australia.
Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, 815 Hwarangro, Nowon-gu, Seoul, 01795, Republic of Korea.
Neurochem Int. 2021 Mar;144:104962. doi: 10.1016/j.neuint.2021.104962. Epub 2021 Jan 16.
The recreational use of N-methyl-D-aspartate (NMDA) antagonist phencyclidine (PCP) and ketamine have grown rapidly due to their psychotomimetic properties. These compounds induce both non-fatal and fatal adverse effects and despite the enhanced regulation, they are continuously synthesized and are being sold in the illegal drug market, including 1-phenylcyclohexan-1-amine hydrochloride (PCA). Therefore, we evaluated its abuse potential through the conditioned-place preference (CPP), self-administration, and locomotor sensitization paradigms. Pretreatment with SCH 2 3390 and haloperidol was also performed during a CPP test. We used ELISA to measure dopamine (DA) levels and western blotting to determine effects on the DA-related proteins as well as on phosphorylated CREB, deltaFosB, and brain-derived neurotrophic factor (BDNF) in the ventral tegmental area (VTA) and nucleus accumbens (NAc). Finally, we examined the effects on brain wave activity using electroencephalography (EEG). PCA induced CPP in mice and was self-administered by rats, suggesting that PCA has rewarding and reinforcing properties. PCA increased locomotor of mice on the first treatment and challenge days. SCH 23390 and haloperidol blocked the CPP. PCA altered the DA, tyrosine hydroxylase, dopamine D1 and D2 receptors as well as p-CREB and deltaFosB. Also, PCA altered the delta and gamma waves in the brain, which were then normalized by SCH 2 3390 and haloperidol. The present findings indicate that PCA may induce abuse potential through the dopaminergic system and probably accompanied with alterations in brain wave activity which is similar to that of other psychotomimetic NMDA antagonists. We advocate thorough monitoring of PCP analogs as they pose potential harm to public health.
由于具有致幻特性，N-甲基-D-天冬氨酸（NMDA）拮抗剂苯环利定（PCP）和氯胺酮的娱乐性使用迅速增加。这些化合物会引起非致命和致命的不良反应，尽管加强了监管，但它们仍在不断合成，并在非法毒品市场上销售，包括 1-苯环己烷-1-胺盐酸盐（PCA）。因此，我们通过条件性位置偏好（CPP）、自我给药和运动敏化范式来评估其滥用潜力。在 CPP 测试中还进行了 SCH 23390 和氟哌啶醇的预处理。我们使用 ELISA 测量多巴胺（DA）水平，并使用 Western blot 确定其对 DA 相关蛋白以及腹侧被盖区（VTA）和伏隔核（NAc）中磷酸化 CREB、deltaFosB 和脑源性神经营养因子（BDNF）的影响。最后，我们使用脑电图（EEG）检查脑电波活动的影响。PCA 在小鼠中诱导 CPP，并被大鼠自我给药，表明 PCA 具有奖赏和强化作用。PCA 增加了小鼠在第一次治疗和挑战日的运动。SCH 23390 和氟哌啶醇阻断 CPP。PCA 改变了 DA、酪氨酸羟化酶、多巴胺 D1 和 D2 受体以及 p-CREB 和 deltaFosB。此外，PCA 改变了大脑中的 delta 和伽马波，SCH 23390 和氟哌啶醇使其恢复正常。这些发现表明，PCA 可能通过多巴胺能系统引起滥用潜力，并且可能伴随着脑电波活动的改变，这与其他致幻性 NMDA 拮抗剂相似。我们主张对 PCP 类似物进行彻底监测，因为它们可能对公共健康造成潜在危害。
