Dissanayake Dilshani W N, Zachariou Margarita, Marsden Charles A, Mason Robert
Department of Physiology, Faculty of Medicine, University of Colombo, Kynsey Road, Colombo 08, Sri Lanka.
Brain Res. 2009 Nov 17;1298:153-60. doi: 10.1016/j.brainres.2009.08.032. Epub 2009 Aug 20.
Sensory gating can be assessed using an auditory conditioning (C)-test (T) paradigm which measures the reduction in the auditory-evoked response produced by a test stimulus following a conditioning stimulus. Schizophrenic patients demonstrate absence of gating while dysfunction in glutamatergic neurotransmission is implicated in the pathophysiology of schizophrenia. This study examined the effect of the glutamate receptor antagonist, phencyclidine (PCP) on auditory gating in the CA3 region and dentate gyrus (DG) of rat hippocampus and medial prefrontal cortex (mPFC). Local field potential (LFP) activity was recorded simultaneously from CA3, DG and mPFC in isoflurane anaesthetised Lister hooded rats using in vivo electrophysiology. Paired auditory stimuli were presented binaurally over 128 trials. The effect of PCP (1 mg/kg, i.p.) on gating of the N2 LFP wave was assessed as the test:conditioning response amplitude ratio (T/C ratio); a value of < or =50% was indicative of gating. Auditory gating of the N2 wave was observed in the CA3, DG and mPFC. PCP disrupted gating in all three areas with significant increases in test amplitudes (P<0.001). Clozapine (5 mg/kg i.p) prevented the auditory gating deficits induced by PCP in the CA3, DG and mPFC. This study shows that PCP disrupts sensory gating in the CA3, DG and mPFC in the isoflurane anaesthetised rat. Similar deficits are observed in schizophrenic patients and the current method may provide an animal model with good predictive validity, a view substantiated by the fact that clozapine prevented the sensory gating deficits induced by PCP.
感觉门控可通过听觉条件化（C）-测试（T）范式进行评估，该范式测量条件刺激后测试刺激所产生的听觉诱发反应的减少。精神分裂症患者表现出门控缺失，而谷氨酸能神经传递功能障碍与精神分裂症的病理生理学有关。本研究考察了谷氨酸受体拮抗剂苯环利定（PCP）对大鼠海马CA3区、齿状回（DG）及内侧前额叶皮质（mPFC）听觉门控的影响。采用体内电生理学方法，在异氟烷麻醉的利斯特戴帽大鼠中，同时记录CA3区、DG区和mPFC的局部场电位（LFP）活动。通过128次试验双耳呈现配对听觉刺激。将PCP（1mg/kg，腹腔注射）对N2 LFP波门控的影响评估为测试：条件反应幅度比（T/C比）；该值≤50%表明存在门控。在CA3区、DG区和mPFC观察到N2波的听觉门控。PCP破坏了所有三个区域的门控，测试幅度显著增加（P<0.001）。氯氮平（5mg/kg，腹腔注射）可预防PCP在CA3区、DG区和mPFC诱导的听觉门控缺陷。本研究表明，PCP破坏了异氟烷麻醉大鼠CA3区、DG区和mPFC的感觉门控。在精神分裂症患者中也观察到类似缺陷，目前的方法可能提供一种具有良好预测效度的动物模型，氯氮平预防PCP诱导的感觉门控缺陷这一事实证实了这一观点。
