Swerdlow N R, Geyer M A
Department of Psychiatry, UCSD School of Medicine, La Jolla 92093-0804.
Pharmacol Biochem Behav. 1993 Mar;44(3):741-4. doi: 10.1016/0091-3057(93)90193-w.
Prepulse inhibition (PPI) of the acoustic startle response is a measure of sensorimotor gating that is impaired in both schizophrenic patients and in rats treated with dopamine agonists. The disruption of PPI by the dopamine agonist apomorphine (APO) is reversed by antipsychotic agents, including the atypical antipsychotic clozapine. Across a range of compounds, the ability of antipsychotics to restore PPI in APO-treated rats correlates significantly with their clinical potency. Since few animal models predict antipsychotic potency for clozapine, we further characterized the effects of clozapine and the typical antipsychotic haloperidol on APO-disrupted and baseline PPI in rats. The APO-induced disruption of PPI caused by intense (15 dB over background) prepulses was reversed in a dose-dependent manner by both clozapine and haloperidol. When weak (1-5 dB over background) prepulses were used, clozapine and haloperidol increased baseline PPI in control animals. Both APO-disrupted and baseline PPI may be useful in screening both typical and atypical antipsychotic agents.
听觉惊吓反应的前脉冲抑制（PPI）是一种感觉运动门控的测量指标，在精神分裂症患者和用多巴胺激动剂治疗的大鼠中均受损。多巴胺激动剂阿扑吗啡（APO）对PPI的破坏可被包括非典型抗精神病药物氯氮平在内的抗精神病药物逆转。在一系列化合物中，抗精神病药物在APO处理的大鼠中恢复PPI的能力与其临床效力显著相关。由于很少有动物模型能预测氯氮平的抗精神病效力，我们进一步研究了氯氮平和典型抗精神病药物氟哌啶醇对大鼠APO破坏的PPI和基线PPI的影响。由强烈（比背景高15 dB）前脉冲引起的APO诱导的PPI破坏，可被氯氮平和氟哌啶醇以剂量依赖的方式逆转。当使用微弱（比背景高1 - 5 dB）前脉冲时，氯氮平和氟哌啶醇可增加对照动物的基线PPI。APO破坏的PPI和基线PPI在筛选典型和非典型抗精神病药物时可能都有用。
