Bakshi V P, Geyer M A
Department of Neuroscience, University of California at San Diego, La Jolla, CA 92093-0804, USA.
Psychopharmacology (Berl). 1995 Nov;122(2):198-201. doi: 10.1007/BF02246096.
Prepulse inhibition (PPI) of the startle reflex provides an operational measure of sensorimotor gating. Deficits in PPI are observed in schizophrenia patients and can be modelled in animals by administration of noncompetitive NMDA antagonists such as phencyclidine (PCP) or dizocilpine (MK-801). Previous studies indicate that the atypical antipsychotic clozapine restores PPI in PCP-treated animals while the typical antipsychotic haloperidol does not. Olanzapine (LY170053) is a novel putative atypical antipsychotic that shares many pharmacological and behavioral properties with clozapine. The present study assessed the ability of olanzapine (0, 1.25, 2.5, 5.0 or 10.0 mg/kg) to antagonize deficits in PPI produced by PCP (1.5 mg/kg) and dizocilpine (0.1 mg/kg). At the two highest doses, olanzapine significantly increased PPI in PCP- and dizocilpine-treated animals without affecting PPI or baseline startle reactivity by itself. These results support the notion that olanzapine is functionally similar to clozapine and may have utility as an atypical antipsychotic agent.
惊吓反射的前脉冲抑制（PPI）为感觉运动门控提供了一种可操作的测量方法。精神分裂症患者存在PPI缺陷，通过给予非竞争性NMDA拮抗剂如苯环利定（PCP）或地佐环平（MK - 801）可在动物中模拟出这种缺陷。先前的研究表明，非典型抗精神病药物氯氮平可恢复PCP处理动物的PPI，而典型抗精神病药物氟哌啶醇则不能。奥氮平（LY170053）是一种新型的非典型抗精神病药物，与氯氮平具有许多药理学和行为学特性。本研究评估了奥氮平（0、1.25、2.5、5.0或10.0 mg/kg）拮抗PCP（1.5 mg/kg）和地佐环平（0.1 mg/kg）所致PPI缺陷的能力。在两个最高剂量下，奥氮平显著增加了PCP和地佐环平处理动物的PPI，而其本身不影响PPI或基线惊吓反应性。这些结果支持奥氮平在功能上与氯氮平相似且可能作为非典型抗精神病药物有用的观点。
