Keith V A, Mansbach R S, Geyer M A
Department of Psychiatry, University of California, San Diego, School of Medicine, La Jolla 92093.
Biol Psychiatry. 1991 Sep 15;30(6):557-66. doi: 10.1016/0006-3223(91)90025-h.
Prepulse inhibition of acoustic or tactile startle (PPI), a form of sensorimotor gating, occurs when a weak prestimulus precedes a startling stimulus and inhibits the startle response. Studies of PPI have revealed that schizophrenic patients exhibit a deficit in this form of sensorimotor gating. In rats, PPI is blocked by dopamine agonists such as apomorphine or quinpirole, effects that are antagonized by haloperidol. Phencyclidine (PCP) has been suggested as a possible model psychotogen and produces a deficit in PPI that is similar to what is observed in schizophrenic patients. Dizocilpine is an anticonvulsant drug that, like PCP, is a noncompetitive antagonist of N-methyl-D-aspartate (NMDA)-induced excitations in brain and also disrupts PPI. In the present study, PPI of acoustic and tactile startle was measured in male Sprague-Dawley rats after injections of 5.0 mg/kg PCP with or without pretreatment with 0.02 or 0.1 mg/kg haloperidol, or with 0.5 mg/kg dizocilpine with or without pretreatment with 0.1 mg/kg haloperidol. The 0.1 mg/kg dose of haloperidol blocks the effects of apomorphine or quinpirole on PPI in rats. Startle was elicited by noise bursts at 105 or 120 dB or by air-puffs (tactile) and was inhibited by 75 or 85 dB 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. Both NMDA antagonists significantly reduced the amount of PPI induced by the 75 dB prestimulus, independently of the level of startle responses elicited by the startle stimuli. Haloperidol did not block the disruption of PPI induced by either PCP or dizocilpine. In addition, PCP was unable to block PPI when the 85 rather than the 75 dB prepulse was used to inhibit either acoustic or tactile startle. These results confirm that putative NMDA antagonists inhibit sensorimotor gating in rats and suggest that these effects are not mediated by the activation of central dopamine systems.
听觉或触觉惊跳反应的前脉冲抑制（PPI）是一种感觉运动门控形式，当一个弱的预刺激先于一个惊吓刺激出现并抑制惊跳反应时就会发生。对PPI的研究表明，精神分裂症患者在这种感觉运动门控形式上存在缺陷。在大鼠中，PPI会被多巴胺激动剂如阿扑吗啡或喹吡罗阻断，而这些作用会被氟哌啶醇拮抗。苯环己哌啶（PCP）被认为是一种可能的模型致幻剂，它会导致PPI缺陷，这与在精神分裂症患者中观察到的情况相似。地佐环平是一种抗惊厥药物，与PCP一样，它是大脑中N-甲基-D-天冬氨酸（NMDA）诱导兴奋的非竞争性拮抗剂，也会破坏PPI。在本研究中，对雄性Sprague-Dawley大鼠注射5.0mg/kg PCP，无论是否预先用0.02或0.1mg/kg氟哌啶醇预处理，或者注射0.5mg/kg地佐环平，无论是否预先用0.1mg/kg氟哌啶醇预处理，然后测量其听觉和触觉惊跳反应的PPI。0.1mg/kg剂量的氟哌啶醇会阻断阿扑吗啡或喹吡罗对大鼠PPI的作用。通过105或120dB的噪声脉冲或吹气（触觉）引发惊跳反应，并通过在惊跳刺激前100毫秒呈现的75或85dB预脉冲刺激来抑制。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水平的惊跳反应。两种NMDA拮抗剂均显著降低了由75dB预刺激诱导的PPI量，与惊跳刺激引发的惊跳反应水平无关。氟哌啶醇并未阻断PCP或地佐环平诱导的PPI破坏。此外，当使用85dB而不是75dB预脉冲来抑制听觉或触觉惊跳反应时，PCP无法阻断PPI。这些结果证实了假定的NMDA拮抗剂会抑制大鼠的感觉运动门控，并表明这些作用不是由中枢多巴胺系统的激活介导的。
