Phencyclidine Disrupts the Auditory Steady State Response in Rats.
Phencyclidine Disrupts the Auditory Steady State Response in Rats.
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DOI：
10.1371/journal.pone.0134979
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Morzorati SL
中科院分区：
文献类型：
--
作者：
Leishman E;O'Donnell BF;Millward JB;Vohs JL;Rass O;Krishnan GP;Bolbecker AR;Morzorati SL
精神分裂症（SZ）患者脑电图（EEG）中的听觉稳态反应（ASSR）通常降低，特别是对40 Hz刺激。γ频率ASSR缺陷归因于N-甲基-D-天冬氨酸受体（NMDAR）功能低下。我们测试了NMDAR拮抗剂苯环己哌啶（PCP）是否在大鼠中产生类似的ASSR缺陷。通过覆盖听觉皮层和颅骨顶部的颅内电极记录清醒大鼠的EEG。在10、20、30、40、50和55 Hz下记录对咔哒声列车的ASSR，并通过ASSR平均功率（MP）和锁相因子（PLF）进行测量。在实验1中，评估了不同剂量的PCP（1.0、2.5和4.0 mg/kg）对12只大鼠ASSR的影响。在实验2中，在基线、急性注射（5 mg/kg）后、亚慢性连续给药（5 mg/kg/天）两周后和停药一周后，比较了PCP治疗大鼠和对照大鼠的ASSR。PCP急性给药增加PLF和MP在频率低于50 Hz的刺激，并在较高的频率在听觉皮层网站的反应下降。急性给药在顶点部位的影响不太明显，在20 Hz以上的频率下观察到PLF或MP减少。五氯苯酚剂量越高，急性效应越大。亚慢性五氯苯酚给药后未观察到一致的影响。这些数据表明，急性给药PCP，一种NMDAR拮抗剂，在低频刺激下产生ASSR同步性和功率的增加，以及高频（> 40 Hz）ASSR活动的减少。另一方面，亚慢性、连续给予PCP对ASSR的影响很小。因此，虽然ASSR对NMDAR拮抗剂高度敏感，但其作为SZ和其他疾病中NMDAR功能减退的跨物种生物标志物的翻译效用可能取决于剂量和时间表。
The Auditory Steady-State Response (ASSR) in the electroencephalogram (EEG) is usually reduced in schizophrenia (SZ), particularly to 40 Hz stimulation. The gamma frequency ASSR deficit has been attributed to N-methyl-D-aspartate receptor (NMDAR) hypofunction. We tested whether the NMDAR antagonist, phencyclidine (PCP), produced similar ASSR deficits in rats. EEG was recorded from awake rats via intracranial electrodes overlaying the auditory cortex and at the vertex of the skull. ASSRs to click trains were recorded at 10, 20, 30, 40, 50, and 55 Hz and measured by ASSR Mean Power (MP) and Phase Locking Factor (PLF). In Experiment 1, the effect of different subcutaneous doses of PCP (1.0, 2.5 and 4.0 mg/kg) on the ASSR in 12 rats was assessed. In Experiment 2, ASSRs were compared in PCP treated rats and control rats at baseline, after acute injection (5 mg/kg), following two weeks of subchronic, continuous administration (5 mg/kg/day), and one week after drug cessation. Acute administration of PCP increased PLF and MP at frequencies of stimulation below 50 Hz, and decreased responses at higher frequencies at the auditory cortex site. Acute administration had a less pronounced effect at the vertex site, with a reduction of either PLF or MP observed at frequencies above 20 Hz. Acute effects increased in magnitude with higher doses of PCP. Consistent effects were not observed after subchronic PCP administration. These data indicate that acute administration of PCP, a NMDAR antagonist, produces an increase in ASSR synchrony and power at low frequencies of stimulation and a reduction of high frequency (> 40 Hz) ASSR activity in rats. Subchronic, continuous administration of PCP, on the other hand, has little impact on ASSRs. Thus, while ASSRs are highly sensitive to NMDAR antagonists, their translational utility as a cross-species biomarker for NMDAR hypofunction in SZ and other disorders may be dependent on dose and schedule.