FAILURE OF HALOPERIDOL TO BLOCK THE EFFECTS OF PHENCYCLIDINE AND DIZOCILPINE ON PREPULSE INHIBITION OF STARTLE
FAILURE OF HALOPERIDOL TO BLOCK THE EFFECTS OF PHENCYCLIDINE AND DIZOCILPINE ON PREPULSE INHIBITION OF STARTLE
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DOI：
10.1016/0006-3223(91)90025-h
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发表时间：
1991-09-15
影响因子：
10.6
通讯作者：
GEYER, MA
中科院分区：
文献类型：
--
作者：
KEITH, VA;MANSBACH, RS;GEYER, MA
声学或触觉惊吓的脉冲前抑制(PPI)是感觉运动门控的一种形式，当微弱的前刺激先于令人震惊的刺激并抑制惊吓反应时发生。对PPI的研究表明，精神分裂症患者在这种形式的感觉运动门控方面表现出缺陷。在大鼠中，PPI可被阿朴吗啡或喹比罗等多巴胺激动剂阻断，这些作用可被氟哌啶醇拮抗。苯环利定(PCP)被认为是一种可能的模式精神诱因，它产生的PPI缺陷与精神分裂症患者的PPI缺陷相似。地佐西平是一种抗惊厥药物，与PCP一样，是N-甲基-D-天冬氨酸(NMDA)诱导的脑内兴奋的非竞争性拮抗剂，也可以扰乱PPI。给雄性SD大鼠注射5.0 mg/kg五氯苯酚(PCP)，加或不加0.02或0.1 mg/kg氟哌啶醇，或加0.5 mg/kg地佐西平加或不加0.1 mg/kg氟哌啶醇，测定大鼠听觉和触觉惊厥的PPI。0.1 mg/kg剂量的氟哌啶醇可阻断阿朴吗啡或喹比罗对大鼠PPI的影响。惊厥可由105或120分贝的噪声爆发或喷气(触觉)引起，并可被在惊吓刺激前100毫秒出现的75或85分贝预脉冲刺激抑制。不同的激发刺激在对照组和药物处理组的动物中产生了不同程度的惊吓。两种NMDA拮抗剂均可显著降低75分贝前刺激诱发的PPI，与惊吓刺激引起的惊吓反应程度无关。氟哌啶醇不能阻断PCP或地佐西平对PPI的阻断作用。此外，当使用85分贝的预脉冲而不是75分贝的预脉冲来抑制声学或触觉惊吓时，PCP不能阻断PPI。这些结果证实了可能的NMDA拮抗剂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所介导的。
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.