de Bruin N M, Ellenbroek B A, Cools A R, Coenen A M, van Luijtelaar E L
NICI/Department of Comparative and Physiological Psychology, University of Nijmegen, The Netherlands.
Psychopharmacology (Berl). 1999 Feb;142(1):9-17. doi: 10.1007/s002130050856.
Schizophrenic patients suffer from deficits in information processing. Patients show both a decrease in P50 gating [assessed in the conditioning-testing (C-T) paradigm] and prepulse inhibition (PPI), two paradigms that assess gating. These two paradigms might have a related underlying neural substrate. Gating, as measured in both the C-T paradigm (the gating of a component of the auditory evoked potential (AEP)], and PPI can easily be measured in animals as well as in humans. This offers the opportunity to model these information processing paradigms in animals in order to investigate the effects of neurotransmitter manipulations in the brain. In order to validate the animal model for disturbances in AEP gating, d-amphetamine (0.5 and 1 mg/kg, i.p.) was administered. Gating of an AEP component was changed due to injection of d-amphetamine (1 mg/kg) in the same way as seen in schizophrenic patients: both the amplitude to the conditioning click and the gating were significantly reduced. Next, the effect of the N-methyl-D-aspartate (NMDA) antagonist ketamine (2.5 and 10 mg/kg, i.p.) was investigated to assess its effects in the two gating paradigms. It was found that ketamine (10 mg/kg) did not affect gating as measured with components of the AEP. However, ketamine (10 mg/kg) disrupted PPI of the startle response to the extent that prepulse facilitation occurred. Firstly, it is concluded that AEP gating was disrupted by d-amphetamine and not by ketamine. Secondly, PPI and the C-T paradigm reflect distinct inhibitory sensory processes, since both paradigms are differentially influenced by ketamine.
精神分裂症患者存在信息处理缺陷。患者在P50门控（在条件-测试范式中评估）和前脉冲抑制（PPI）方面均表现出下降，这两种范式均用于评估门控。这两种范式可能具有相关的潜在神经基质。在条件-测试范式（听觉诱发电位（AEP）成分的门控）以及PPI中测量的门控，在动物和人类中都很容易测量。这为在动物中模拟这些信息处理范式提供了机会，以便研究大脑中神经递质操纵的影响。为了验证AEP门控障碍的动物模型，给予了d-苯丙胺（0.5和1mg/kg，腹腔注射）。注射d-苯丙胺（1mg/kg）后，AEP成分的门控发生了变化，与精神分裂症患者的情况相同：条件性点击的幅度和门控均显著降低。接下来，研究了N-甲基-D-天冬氨酸（NMDA）拮抗剂氯胺酮（2.5和10mg/kg，腹腔注射）的作用，以评估其在两种门控范式中的效果。结果发现，氯胺酮（10mg/kg）对AEP成分测量的门控没有影响。然而，氯胺酮（10mg/kg）破坏了惊吓反应的PPI，以至于出现了前脉冲促进。首先，可以得出结论，d-苯丙胺而非氯胺酮破坏了AEP门控。其次，PPI和条件-测试范式反映了不同的抑制性感觉过程，因为这两种范式受氯胺酮的影响不同。
