Ketamine dose-dependently induces high-frequency oscillations in the nucleus accumbens in freely moving rats
Ketamine dose-dependently induces high-frequency oscillations in the nucleus accumbens in freely moving rats
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DOI：
10.1016/j.biopsych.2006.01.020
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发表时间：
2006-12-01
影响因子：
10.6
通讯作者：
Garcia, Rene
中科院分区：
文献类型：
--
作者：
Hunt, Mark Jeremy;Raynaud, Beryl;Garcia, Rene
背景：在人类中，麻醉下剂量的氯胺酮和从氯胺酮麻醉中恢复与精神病患者的行为有关。在啮齿类动物中，氯胺酮会产生多动、刻板印象和不正常的社会互动，用于模拟精神分裂症的某些特征。越来越多的证据表明伏隔核(NAC)的异常活动与精神分裂症的病理生理机制有关。方法：我们观察了ip氯胺酮(10、25、50和200 mg/kg)和d-苯丙胺(3 mg/kg)对啮齿动物伏核(NAC)局部场电位的影响。结果：NAC记录到的局部场电位存在自发性高频振荡(HFO)(140~180 Hz)。氯胺酮剂量依赖地诱导与行为多动相关的HFO迅速和显著增加。同样，在氯胺酮麻醉恢复过程中，HFO也有较大的增加。相反，d-苯丙胺诱导的运动活动仅产生轻微的HFO值增加。我们认为，氯胺酮诱导的HfO异常增加形成了这种精神分裂症模型中复杂的神经变化。氯胺酮诱导的HFO增加，尽管与多动的时间动力学相似，但在功能上可能与运动增加无关。
Background: In humans, subanesthetic doses of ketamine and recovery from ketamine anesthesia are associated with psychotic-like behavior. in rodents, ketamine produces hyperactivity, stereotypies, and abnormal social interaction used to model certain features of schizophrenia. Increasing evidence has implicated aberrant activity in the nucleus accumbens (NAc) with the pathophysiology of schizophrenia.Methods: Here, we examined the effect of an IP injection of ketamine (10, 25 50, and 200 mg/kg) and d-amphetamine (3 mg/kg) on local field potentials in the rodent NAc. Locomotor activity was recorded simultaneously.Results: Spontaneous high-frequency oscillations (HFO) (140-180 Hz) were present in local field potentials recordedfrom the NAc. Ketamine dose-dependently induced rapid and substantial increases in HFO that correlated with behavioral hyperactivity. Similarly, large increases in HFO occurred during recovery from ketamine anesthesia. In contrast, d-amphetamine, which induced locomotor activity, produced only small increases in HFO.Conclusions. We propose that ketamine-induced abnormal increases in HFO form pan of the complex neurological changes in this model of schizophrenia. Ketamine-induced increases in HFO, although sharing similar temporal dynamics to hyperactivity, may not be functionally related to increased movement.