Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA; Ross University School of Veterinary Medicine, St. Kitts, Saint Kitts and Nevis.
Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, USA.
Exp Neurol. 2019 Mar;313:26-36. doi: 10.1016/j.expneurol.2018.12.001. Epub 2018 Dec 3.
Synthetic cathinones, often marketed as 'bath salts', have been reported to induce an excited delirium syndrome with characteristic symptoms such as paranoid, hallucination and even aggression. 3,4-Methylenedioxypyrovalerone (MDPV), a norepinephrine-dopamine reuptake inhibitor (NDRI), is one of the psychoactive ingredients in bath salts. The present study utilized cortical EEG and brain microdialysis in rats to compare the effects of MDPV (0.25, 1 and 2 mg/kg, i.p.) with the hallucinogenic drugs MK-801 (0.05, 0.1 and 0.5 mg/kg, i.p.) and ketamine (5, 15 and 25 mg/kg, i.p.). Results revealed that MDPV similar to MK-801 and ketamine caused a dose-dependent increase in the cortical EEG synchronization. In addition, all three drugs produced an increase in DA efflux in the prefrontal cortex (FCx). However, there existed difference between the three drugs. In contrast to MDPV, MK-801 and ketamine had only moderate or little effects on DA efflux in the nucleus accumbens (NAcc). Except for ketamine, the effects of MDPV and MK-801 on EEG synchronization were blocked by the D receptor antagonist SCH23990 (0.1 mg/kg, i.p.) and D receptor antagonist sulpiride (100 mg/kg, i.p.). SCH23990 or sulpiride had no effect on ketamine-induced increases in EEG synchronization. In summary, the present comparative studies suggest that DA in the FCx, but unlikely the NAcc, exerts a critical role in increasing EEG synchronization associated with the excited delirium syndrome. Neural circuits consisting of glutamatergic and GABAergic neurons responsible for the hallucinogenic effect are discussed in the context of hyperdopamine and dysconnection theories for hallucinatory behaviors.
合成卡西酮，常被宣传为“浴盐”，据报道会引起兴奋性谵妄综合征，其特征症状包括偏执、幻觉甚至攻击行为。3,4-亚甲基二氧吡咯戊酮（MDPV）是浴盐中的一种致幻成分，是去甲肾上腺素-多巴胺再摄取抑制剂（NDRI）。本研究利用皮质脑电图和大鼠脑微透析技术，比较了 MDPV（0.25、1 和 2mg/kg，ip）与致幻药物 MK-801（0.05、0.1 和 0.5mg/kg，ip）和氯胺酮（5、15 和 25mg/kg，ip）的作用。结果表明，MDPV 与 MK-801 和氯胺酮相似，可引起皮质脑电图同步化的剂量依赖性增加。此外，这三种药物都使前额叶皮层（FCx）中的 DA 外排量增加。然而，这三种药物之间存在差异。与 MDPV 不同，MK-801 和氯胺酮对伏隔核（NAcc）中的 DA 外排量只有中度或较小的影响。除氯胺酮外，D 受体拮抗剂 SCH23990（0.1mg/kg，ip）和 D 受体拮抗剂舒必利（100mg/kg，ip）可阻断 MDPV 和 MK-801 对 EEG 同步化的作用。SCH23990 或舒必利对氯胺酮引起的 EEG 同步化增加没有影响。综上所述，本研究表明，FCx 中的 DA 而不是 NAcc 对与兴奋性谵妄综合征相关的 EEG 同步化增加起着关键作用。讨论了与致幻行为相关的谷氨酸能和 GABA 能神经元的神经回路，涉及到致幻行为的高多巴胺和连接中断理论。
