Comparison of the effects of acute and chronic administration of ketamine on hippocampal oscillations: relevance for the NMDA receptor hypofunction model of schizophrenia.
Comparison of the effects of acute and chronic administration of ketamine on hippocampal oscillations: relevance for the NMDA receptor hypofunction model of schizophrenia.
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DOI：
10.1007/s00429-011-0351-8
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发表时间：
2012-04
影响因子：
3.1
通讯作者：
Kocsis, Bernat
中科院分区：
文献类型：
--
作者：
Kittelberger, Kara;Hur, Elizabeth E.;Sazegar, Saba;Keshavan, Vidya;Kocsis, Bernat
GABA能中间神经元网络的适当组织和功能对于许多认知过程是必不可少的，并且这些系统中的异常在精神分裂症患者中已被记录。海马体的记忆功能取决于θ和γ范围内的两种主要振荡模式，这两种模式都需要表达小白蛋白的快速放电中间神经元网络的完整功能。我们研究的能力，急性和慢性管理的NMDA受体拮抗剂，重演振荡功能障碍观察精神分裂症。在自由活动的大鼠中，急性注射MK 801或氯胺酮增加海马CA 1和齿状回的γ功率。θ峰向更高频率移动，而平均5-10 Hz θ功率在CA 1中下降了24%，并且在齿状回中保持较高。在乌拉坦麻醉下，发现脑干刺激引起的CA 1 γ的强烈增加和θ功率的降低。与急性实验相反，氯胺酮的长期给药在治疗后2-4周引起γ和θ振荡的稳定下降。两种模型之间的另一个重要差异是，急性注射的影响比慢性治疗后的变化更稳健。氯胺酮的长期给药也导致可检测到的小白蛋白中间神经元的数量减少。然而，个体间差异的组织学检查表明，在氯胺酮治疗组内，小白蛋白神经元的进一步减少与振荡的加强相关。这一发现与人类精神分裂症的振荡异常一致，进一步验证了NMDA受体功能减退假说。
The proper organization and function of GABAergic interneuron networks is essential for many cognitive processes and abnormalities in these systems have been documented in schizophrenic patients. The memory function of the hippocampus depends on two major patterns of oscillations in the theta and gamma ranges, both requiring the intact functioning of the network of fast-firing interneurons expressing parvalbumin. We examined the ability of acute and chronic administration of NMDA receptor antagonists to recapitulate the oscillatory dysfunctions observed in schizophrenia. In freely moving rats, acute injection of MK801 or ketamine increased gamma power in both CA1 and dentate gyrus of the hippocampus. Theta peak shifted to higher frequencies whereas the average 5–10 Hz theta power decreased by 24% in CA1 and remained high in the dentate gyrus. Strong increase in CA1 gamma and decrease in theta power triggered by brainstem stimulation were found under urethane anesthesia. In contrast to acute experiments, chronic administration of ketamine caused a steady decline in both gamma and theta oscillations, 2–4 weeks after treatment. A further important difference between the two models was that the effects of acute injection were more robust than the changes after chronic treatment. Chronic administration of ketamine also lead to decrease in the number of detectable parvalbumin interneurons. Histological examination of interindividual differences indicated however that within the ketamine treated group a further decrease in parvalbumin neurons correlated with strengthening of oscillations. The findings are consistent with abnormalities of oscillations in human schizophrenia and further validate the NMDA receptor hypofunction hypothesis.
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影响因子：
3.7
作者：
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作者：
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