Suemaru Katsuya, Kohnomi Shuntaro, Umeda Kenta, Araki Hiroaki
Department of Clinical Pharmacology and Pharmacy, Neuroscience, Ehime University Graduate School of Medicine, Shitsukawa, Toon 791-0295, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2008 Jun;28(3):121-6.
The prepulse inhibition (PPI) is a phenomenon in which a weak prepulse attenuates the response to a subsequent startling stimulus. The PPI, a model of sensorimotor gating, is deficient in patients with schizophrenia and some other psychiatric disorders. In rodents, PPI can be disrupted by methamphetamine or phencyclidine, which causes psychotomimetic symptoms, and the dopaminergic agonist-induced PPI is reversed by dopamine D2 receptor antagonists and a dopaminergic partial agonist aripiprazole. However, in general, the glutamate receptor antagonist-induced PPI is reversed by atypical antipsychotics such as clozapine, but not by typical antipsychotics such as haloperidol. Therefore, PPI is believed to have face, construct, and predictive validity for the PPI disruption in schizophrenia, and it is widely used as a model to study the neurobiology of this disorder and for screening antipsychotics. Recently, various inbred mouse strains and genetically modified mouse lines have been examined and the studies using PPI indicated the involvement of various neurotransmitters such as dopamine, glutamate, serotonin, GABA and neuropeptide in the biological basis of sensorimotor gating. In addtition, mood stabilizers such as valproate and lamotrigine or alpha7 nicotinic receptor agonists have reported to reverse the PPI disruption.
前脉冲抑制（PPI）是一种现象，即微弱的前脉冲会减弱对随后惊吓刺激的反应。PPI作为一种感觉运动门控模型，在精神分裂症患者和其他一些精神疾病患者中存在缺陷。在啮齿动物中，甲基苯丙胺或苯环利定可破坏PPI，这会导致拟精神病症状，多巴胺能激动剂诱导的PPI可被多巴胺D2受体拮抗剂和多巴胺能部分激动剂阿立哌唑逆转。然而，一般来说，谷氨酸受体拮抗剂诱导的PPI可被非典型抗精神病药物如氯氮平逆转，但不能被典型抗精神病药物如氟哌啶醇逆转。因此，PPI被认为对精神分裂症中的PPI破坏具有表面效度、结构效度和预测效度，并且它被广泛用作研究该疾病神经生物学和筛选抗精神病药物的模型。最近，人们对各种近交系小鼠和基因工程小鼠品系进行了研究，使用PPI的研究表明多巴胺、谷氨酸、5-羟色胺、γ-氨基丁酸和神经肽等多种神经递质参与了感觉运动门控的生物学基础。此外，据报道丙戊酸盐和拉莫三嗪等情绪稳定剂或α7烟碱受体激动剂可逆转PPI破坏。
