Uimyung Research Institute for Neuroscience, Department of Pharmacy, Sahmyook University, Seoul, Republic of Korea.
Centre for Neuroscience and Regenerative Medicine, Faculty of Science, University of Technology Sydney, Ultimo, New South Wales, Australia.
Addict Biol. 2021 Jul;26(4):e12981. doi: 10.1111/adb.12981. Epub 2020 Nov 1.
Novel psychoactive substances remain the popular recreational drugs of use over the years. They continue to bypass government restrictions due to their synthesis and modifications. Recent additions to the lists are the 4-F-PCP and 4-Keto-PCP, analogs of the drug phencyclidine (PCP) known to induce adverse effects and abuse potential. However, studies on the abuse potential of 4-F-PCP and 4-Keto-PCP remain scarce. The rewarding and reinforcing effects of the drugs were assessed using conditioned place preference (CPP), self-administration, and locomotor sensitization tests. Dopamine (DA) receptor antagonists (SCH23390 and haloperidol) were administered during CPP to evaluate the involvement of the mesolimbic dopaminergic system. DA-related protein expression in the nucleus accumbens (NAcc) and ventral tegmental area (VTA) was measured. Additionally, phosphorylated cyclic-adenosine monophosphate-activated protein (AMP) response element-binding (p-CREB) protein, deltaFosB (∆FosB), and brain-derived neurotrophic factor (BDNF) protein levels in the NAcc were measured to assess the addiction neural plasticity effect of the drugs. Both 4-F-PCP and 4-Keto-PCP-induced CPP and self-administration; however, only 4-F-PCP elicited locomotor sensitization. Treatment with DA receptor antagonists (SH23390 and haloperidol) inhibited the 4-F- and 4-Keto-induced CPP. Both substances altered the levels of DA receptor D1 (DRD1), thyroxine hydroxylase (TH), DA receptor D2 (DRD2), p-CREB, ∆FosB, and BDNF. The results suggest that 4-F-PCP and 4-Keto-PCP may induce abuse potential in rodents via alterations in dopaminergic system accompanied by addiction neural plasticity.
新型精神活性物质多年来一直是流行的消遣性药物。由于它们的合成和修饰，它们继续绕过政府的限制。最近添加到清单中的是 4-F-PCP 和 4-Keto-PCP，它们是苯环利定（PCP）的类似物，已知会引起不良反应和滥用潜力。然而，关于 4-F-PCP 和 4-Keto-PCP 的滥用潜力的研究仍然很少。使用条件位置偏好（CPP）、自我给药和运动敏化测试评估药物的奖赏和强化作用。在 CPP 期间给予多巴胺（DA）受体拮抗剂（SCH23390 和氟哌啶醇），以评估中脑边缘多巴胺能系统的参与情况。测量伏隔核（NAcc）和腹侧被盖区（VTA）中的多巴胺相关蛋白表达。此外，还测量了 NAcc 中的磷酸化环腺苷酸激活蛋白（AMP）反应元件结合（p-CREB）蛋白、DeltaFosB（∆FosB）和脑源性神经营养因子（BDNF）蛋白水平，以评估药物的成瘾神经可塑性效应。4-F-PCP 和 4-Keto-PCP 均诱导 CPP 和自我给药；然而，只有 4-F-PCP 引起运动敏化。DA 受体拮抗剂（SH23390 和氟哌啶醇）的治疗抑制了 4-F-和 4-Keto 诱导的 CPP。这两种物质改变了多巴胺受体 D1（DRD1）、甲状腺素羟化酶（TH）、多巴胺受体 D2（DRD2）、p-CREB、∆FosB 和 BDNF 的水平。结果表明，4-F-PCP 和 4-Keto-PCP 可能通过改变伴随成瘾神经可塑性的多巴胺能系统在啮齿动物中引起滥用潜力。
