Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, China.
Department of Medical Psychology and Medical Ethics, School of Basic Medical Sciences, Shandong University, Jinan, Shandong 250012, China.
Pharmacol Biochem Behav. 2019 Sep;184:172742. doi: 10.1016/j.pbb.2019.172742. Epub 2019 Jul 23.
Ketamine has become increasingly popular in adolescent drug abusers worldwide. Meanwhile, alcohol is usually used by ketamine users. However, little work has been conducted to examine the chronic combined effects of ketamine and ethanol on adolescent brain. Here we probed into the effects of chronic administration of ketamine at recreational doses alone or combined with ethanol on behaviors and neuron damage in an adolescent rat model. 28-day old rats were treated with either 20 or 30 mg/kg ketamine plus or not plus 10% ethanol daily for 21 days. Depressive like behaviors, anxiety like behavior and memory impairment were tested using open field test, forced swimming test, elevated plus maze and Morris water maze. Apoptosis in prefrontal cortex (PFC) and hippocampus (HIP) were determined by the TdT-mediated dUTP Nick-End Labeling (TUNEL) and protein and mRNA levels of caspase-3, Bax and Bcl-2. Results show that co-application of ketamine and ethanol significantly increased immobility time in the forced swimming test, up-regulated TUNEL positive cells and both protein and mRNA expressions of caspase-3 and Bax, compared with the control group and ketamine and ethanol use alone groups in the PFC, but not in the HIP. Our study suggests that chronic co-administration of ketamine and ethanol results in depressive-like behavior and the caspase-dependent apoptosis in the PFC of adolescent rats' brains.
氯胺酮在全世界青少年药物滥用者中越来越受欢迎。同时，酒精通常是氯胺酮使用者使用的。然而，很少有工作研究慢性联合使用氯胺酮和乙醇对青少年大脑的影响。在这里，我们探讨了在青少年大鼠模型中，单独使用或联合使用娱乐剂量的氯胺酮和乙醇对行为和神经元损伤的慢性给药的影响。28 天大的大鼠每天接受 20 或 30mg/kg 氯胺酮加或不加 10%乙醇治疗 21 天。使用旷场试验、强迫游泳试验、高架十字迷宫和 Morris 水迷宫测试抑郁样行为、焦虑样行为和记忆障碍。通过末端转移酶介导的 dUTP 缺口末端标记（TUNEL）和 caspase-3、Bax 和 Bcl-2 的蛋白和 mRNA 水平来确定前额叶皮层（PFC）和海马（HIP）中的细胞凋亡。结果表明，与对照组和氯胺酮和乙醇单独使用组相比，氯胺酮和乙醇的共同应用显著增加了强迫游泳试验中的不动时间，上调了 TUNEL 阳性细胞以及 caspase-3 和 Bax 的蛋白和 mRNA 表达，这在 PFC 中，但不在 HIP 中。我们的研究表明，慢性联合使用氯胺酮和乙醇会导致青少年大鼠大脑中出现抑郁样行为和 caspase 依赖性细胞凋亡。
