Ketamine (KET) is a non-competitive N-Methyl-d-aspartate (NMDA) receptors antagonist that intensifies sensory experiences, prompts hallucinations and delusions, exacerbates previously installed psychosis and disrupts physiological evoked potentials (AEPs). Pharmacologically, KET stimulates glutamate efflux in the medial prefrontal cortex, mainly in the prelimbic (PrL) sub-region. Efferences from this region exert a top-down regulatory control of bottom-up sensory processes either directly or indirectly. In the midbrain, the central nucleus of the inferior colliculus (CIC) plays a fundamental role in the processing of auditory ascending information related to sound localization, sensorimotor gating, and preattentive event-related potentials. Auditory hallucinations elicited during a psychotic outbreak are accompanied by CIC neural activation. Thus, it is possible that NMDA-mediated glutamate neurotransmission in the PrL indirectly modulates CIC neuronal firing. The aim of the present study was to assess the effects of KET on the latency and amplitude of AEPs elicited in the CIC of rats tested during KET effects and following withdrawal from the chronic administration. Changes on emotionally induced by KET treatment were evaluated with the use of the elevated zero maze (EZM). Unlike typical neuroleptics, the atypical antipsychotic clozapine (CLZ) potently blocks the disruption of the sensorimotor gating induced by NMDA antagonists. Therefore, the effects of KET withdrawal on AEPs were challenged with a systemic injection of CLZ. In addition, we further investigated the role of NMDA receptors of the PrL on the AEPs expression recorded in the CIC through intra-PrL infusions of NMDA itself. Our results showed that the processing of sensory information in the CIC is under indirect control of PrL. These data suggest that the long-term KET treatment disrupts the collicular auditory field potentials, possibly through influencing PrL glutamate activity on intrinsic 5-HT mechanisms in the dorsal raphe and CIC.

氯胺酮（KET）是一种非竞争性的N-甲基d-天门冬氨酸（NMDA）受体拮抗剂，可增强感觉体验，引起幻觉和妄想，加剧以前安装的精神病并破坏生理诱发电位（AEP）。在药理上，KET刺激内侧前额叶皮层（主要在前缘（PrL）子区域）中的谷氨酸外排。来自该区域的影响直接或间接施加了自下而上的感觉过程的自上而下的调节控制。在中脑，下丘脑（CIC）的中心核在处理与声音定位，感觉运动门控和注意力不集中的事件相关的电位有关的听觉上升信息中起着基本作用。精神病发作期间引起的听觉幻觉伴有CIC神经激活。因此，PrL中NMDA介导的谷氨酸神经传递可能间接调节CIC神经元放电。本研究的目的是评估KET对在KET作用期间以及退出长期给药后CIC引起的大鼠CIC引起的AEP潜伏期和幅度的影响。通过使用升高的零迷宫（EZM）评估了由KET治疗引起的情绪变化。与典型的抗精神病药不同，非典型抗精神病药氯氮平（CLZ）可以有效阻断NMDA拮抗剂诱导的感觉运动门控的破坏。因此，全身性注射CLZ挑战了KET戒断对AEP的影响。此外，我们进一步研究了PrL的NMDA受体通过内注入NMDA本身在CIC中记录的AEPs表达上的作用。我们的结果表明，CIC中的感官信息处理是在PrL的间接控制下进行的。这些数据表明，长期的KET治疗可能会破坏PrL谷氨酸对背缝和CIC内在的5-HT机制的活性，从而破坏胶体听觉场电位。