Frequent ketamine abuse in adulthood correlates with increased risk of psychosis, as well as cognitive deficits, including disruption of higher-order executive function and memory formation. Although the primary abusers of ketamine are adolescents and young adults, few studies have evaluated its effects on juvenile cognition. Therefore, the current study analyzes the effect of adolescent ketamine exposure on cognitive development. Juvenile mice (4 weeks of age) were exposed to chronic ketamine (20 mg kg−1, i.p. daily) for 14 days. Mice were tested immediately after exposure in the juvenile period (7 weeks of age) and again as adults (12 weeks of age). Measures included electroencephalography (EEG) in response to auditory stimulation, the social choice test, and a 6-arm radial water maze task. Outcome measures include low-frequency EEG responses, event-related potential (ERP) amplitudes, indices of social behavior and indices of spatial working memory. Juvenile exposure to ketamine was associated with electrophysiological abnormalities in adulthood, particularly in induced theta power and the P80 ERP. The social choice test revealed that ketamine-exposed mice failed to exhibit the same age-related decrease in social interaction time as controls. Ketamine-exposed mice outperformed control mice as juveniles on the radial water maze task, but did not show the same age-related improvement as adult controls. These data support the hypothesis that juvenile exposure to ketamine produces long-lasting changes in brain function that are characterized by a failure to progress along normal developmental trajectories.
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机译:成年后经常滥用氯胺酮会增加精神病的风险,以及认知缺陷,包括高阶执行功能和记忆形成的破坏。尽管氯胺酮的主要滥用者是青少年和年轻人,但很少有研究评估其对青少年认知的影响。因此,本研究分析了青少年氯胺酮暴露对认知发展的影响。将幼小小鼠(4周龄)暴露于慢性氯胺酮(每天20 mg mg kg -1 sup>,每天一次)暴露14天。在少年时期(7周龄)暴露后立即对小鼠进行测试,成年后(12周龄)再次对小鼠进行测试。措施包括响应听觉刺激的脑电图(EEG),社交选择测试和6臂放射状水迷宫任务。结果指标包括低频EEG反应,事件相关电位(ERP)幅度,社交行为指数和空间工作记忆指数。青少年接触氯胺酮与成年期的电生理异常有关,特别是在诱导theta功率和P80 ERP中。社交选择测试显示,暴露于氯胺酮的小鼠未能表现出与对照组相同的与年龄相关的社交互动时间减少。暴露于氯胺酮的小鼠在放射状水迷宫任务中的表现优于少年,但未显示与成年对照组相同的年龄相关性改善。这些数据支持以下假设:少年时期接触氯胺酮会导致大脑功能发生持久变化,其特征是无法沿正常发育轨迹进展。
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