Olanzapine and clozapine but not haloperidol reverse subchronic phencyclidine-induced functional hyperactivity of N-methyl-D-aspartate receptors in pyramidal cells of the rat medial prefrontal cortex
Olanzapine and clozapine but not haloperidol reverse subchronic phencyclidine-induced functional hyperactivity of N-methyl-D-aspartate receptors in pyramidal cells of the rat medial prefrontal cortex
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DOI：
10.1016/s0028-3908(03)00033-9
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发表时间：
2003-03-01
影响因子：
4.7
通讯作者：
Wang, RY
中科院分区：
文献类型：
--
作者：
Ninan, I;Jardemark, KE;Wang, RY
在本研究中，我们利用细胞内记录和电压钳技术，研究并比较了奥氮平、氯氮平和氟哌啶醇调节苯环己哌啶（PCP）诱导的大鼠内侧前额皮质（mPFC）锥体细胞的作用的能力。对 PCP 大鼠进行亚慢性治疗（2 mg/kg，每日两次，7 天，48-60 小时停药）产生：(1) 去极化静息膜电位、超极化后缓慢下降 (sAHP) 和尖峰频率适应，(2) N-甲基-D-天冬氨酸 (NMDA) 浓度响应曲线发生变化，但不发生变化。 (+/-)-α-氨基-3-羟基-5-甲基异恶唑-4-丙酸 (AMPA)，左侧，(3) 配对脉冲促进 (PPF) 减少，兴奋性突触后电流方差 (EPSC 方差) 增加，(4) 体外应用 PCP 减少 NMDA 反应阻断。重复使用奥氮平或氯氮平（但不是氟哌啶醇）治疗，完全阻止了上述亚慢性五氯苯酚引起的影响。目前的结果表明，非典型抗精神病药物（APD）氯氮平和奥氮平在预防亚慢性 PCP 诱导的 NMDA 受体功能亢进方面具有共同的特性。 (C) 2003 Elsevier Science Ltd. 保留所有权利。
In the present study, we have investigated and compared the ability of olanzapine, clozapine and haloperidol to modulate phencyclidine (PCP)-induced effect in pyramidal cells of the medial prefrontal cortex (mPFC) of rats using the techniques of intracellular recording and voltage-clamp. Subchronic treatment of rats with PCP (2 mg/kg, b.i.d., 7 days, 48-60 h withdrawal) produced: (1) a depolarized resting membrane potential, a decrease of slow after hyperpolarization (sAHP) and spike frequency adaptation, (2) a shift of the concentration response curve of N-methyl-D-aspartate (NMDA), but not (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), to the left, (3) a decrease of the paired pulse facilitation (PPF) with an increase of excitatory postsynaptic current variance (EPSC variance), and (4) a reduction of the blockade of NMDA response by in vitro application of PCP. Repeated treatment with either olanzapine or clozapine, but not haloperidol, completely prevented the aforementioned subchronic PCP-induced effects. The present results indicate that the atypical antipsychotic drugs (APDs) clozapine and olanzapine share a common property in preventing subchronic PCP-induced functional hyperactivity of NMDA receptors. (C) 2003 Elsevier Science Ltd. All rights reserved.