Mansbach R S, Geyer M A
Department of Pharmacology and Toxicology, Medical College of Virginia.
Neuropsychopharmacology. 1989 Dec;2(4):299-308. doi: 10.1016/0893-133x(89)90035-3.
Prepulse inhibition of the startle response occurs when a weak prestimulus precedes a startling stimulus and decreases the resulting reflex response. Prepulse inhibition provides a measure of sensorimotor gating that is readily assessed in humans and animals. As in event-related-potential models of sensory gating, prepulse inhibition is decreased in schizophrenic patients. In the present study, prepulse inhibition was measured in rats following injections of the N-methyl-D-aspartate (NMDA) antagonists phencyclidine, ketamine, and (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclohepten-5,10-imine (MK-801). Startle was elicited by two different noise intensities or by air-puffs (tactile) and was inhibited by weak acoustic prepulse stimuli presented 100 msec before the startle stimuli. The different eliciting stimuli produced different levels of startle in both control and drug-treated animals, startle being increased by phencyclidine and MK-801. Both phencyclidine (3.0 to 10.0 mg/kg) and MK-801 (0.3 to 1.0 mg/kg) significantly reduced the amount of acoustic prepulse inhibition whereas ketamine did not. These results demonstrate that putative noncompetitive NMDA antagonists disrupt sensorimotor gating in rats and suggest that their effects may provide a model of the deficits in sensory gating exhibited by schizophrenic patients.
当一个弱的预刺激先于一个惊吓刺激出现，并减少由此产生的反射反应时，就会发生惊吓反应的前脉冲抑制。前脉冲抑制提供了一种感觉运动门控的测量方法，这种方法在人类和动物中都很容易评估。与感觉门控的事件相关电位模型一样，精神分裂症患者的前脉冲抑制降低。在本研究中，对注射N-甲基-D-天冬氨酸（NMDA）拮抗剂苯环己哌啶、氯胺酮和（+）-5-甲基-10,11-二氢-5H-二苯并（a,d）-环庚烯-5,10-亚胺（MK-801）后的大鼠进行前脉冲抑制测量。通过两种不同的噪声强度或吹气（触觉）引发惊吓，并通过在惊吓刺激前100毫秒呈现的弱声学前脉冲刺激来抑制惊吓。不同的引发刺激在对照动物和药物处理动物中产生了不同程度的惊吓，苯环己哌啶和MK-801会增加惊吓。苯环己哌啶（3.0至10.0毫克/千克）和MK-801（0.3至1.0毫克/千克）均显著降低了声学前脉冲抑制的量，而氯胺酮则没有。这些结果表明，假定的非竞争性NMDA拮抗剂会破坏大鼠的感觉运动门控，并表明它们的作用可能为精神分裂症患者表现出的感觉门控缺陷提供一个模型。
