Juvenile exposure to ketamine causes delayed emergence of EEG abnormalities during adulthood in mice.
Juvenile exposure to ketamine causes delayed emergence of EEG abnormalities during adulthood in mice.
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DOI：
10.1016/j.drugalcdep.2013.09.017
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发表时间：
2014-01-01
影响因子：
4.2
通讯作者：
Siegel, S. J.
中科院分区：
文献类型：
--
作者：
Featherstone, R. E.;Nagy, L. R.;Hahn, C. G.;Siegel, S. J.
成年后对认知障碍或精神病的易感性增加与青少年药物滥用有关。对成人的研究发现，氯胺酮滥用的常见后果是注意力和记忆力受损以及脑电图变化。相比之下，氯胺酮对青少年大脑的影响尚未得到广泛的测试。这是一个重大遗漏，因为在这一年龄组中经常观察到氯胺酮滥用。幼龄小鼠（4-6周龄）给予氯胺酮（20 mg/kg）14天。在7周龄（幼年）氯胺酮暴露后1周和12周龄（成年）再次评估EEG对听觉刺激的反应。分析EEG的基线活动、事件相关功率和事件相关电位（ERP）。虽然在幼年期未观察到氯胺酮暴露的影响，但当作为成年人重新测试时，在氯胺酮后观察到P20 ERP分量和事件相关伽马功率的振幅显著降低。相比之下，在两个时间点，在氯胺酮暴露的小鼠中观察到事件相关θ的减少。与年龄相关的电生理成分（如P20或事件相关伽马）缺陷可能是由于正常神经成熟的中断。青春期NMDAR信号的减少导致γ振荡和ERP的P20成分的延迟发作中断。此外，青少年氯胺酮滥用后延迟发作的损害表明，可以开发方法来检测和治疗残疾发作前药物暴露的早期影响。
Increased susceptibility to cognitive impairment or psychosis in adulthood is associated with adolescent drug abuse. Studies in adults have identified impairments in attention and memory, and changes in EEG, as common consequences of ketamine abuse. In contrast, the effects of ketamine on the juvenile brain have not been extensively tested. This is a significant omission, since abuse of ketamine is often observed within this age group. Juvenile mice (4–6 weeks of age) were administered ketamine (20 mg/kg) for 14 days. EEG was assessed in response to auditory stimulation both at one week following ketamine exposure at 7 weeks of age (juvenile) and again at 12 weeks of age (adult). EEG was analyzed for baseline activity, event-related power and event-related potentials (ERPs). While no effects of ketamine exposure were observed during the juvenile period, significant reductions in amplitude of the P20 ERP component and event-related gamma power were seen following ketamine when re-tested as adults. In contrast, reductions in event–related theta were seen in ketamine-exposed mice at both time points. Age related deficits in electrophysiological components such as P20 or event-related gamma may be due to an interruption of normal neural maturation. Reduction of NMDAR signaling during adolescence leads to delayed-onset disruption of gamma oscillations and the P20 component of the ERP. Further, delayed onset of impairment following adolescent ketamine abuse suggests that methods could be developed to detect and treat the early effects of drug exposure prior to the onset of disability.
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