Wiley J L
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.
Pharmacol Biochem Behav. 1994 Dec;49(4):1025-8. doi: 10.1016/0091-3057(94)90259-3.
The reduction in magnitude of the startle reflex in response to a loud noise produced by prior presentation of a stimulus of lower intensity is known as prepulse inhibition (PPI). PPI may be disrupted by a variety of drugs, most notably by dopaminergic agonists such as apomorphine and by phencyclidine (PCP), and related noncompetitive N-methyl-D-aspartate (NMDA) antagonists. Apomorphine-induced disruption of PPI is antagonized by both typical and atypical neuroleptics. The present study examined the effects of the atypical neuroleptic, clozapine, alone and in combination with PCP, on PPI in rats. The results of previous studies suggest that disruption of PPI by PCP and similar drugs is not sensitive to antagonism by typical neuroleptics such as haloperidol. The results of the present study show that clozapine's effect on PCP-induced disruption of PPI is also limited. The failure of clinically effective antipsychotics of diverse chemical classes to block the effects of PCP on PPI of acoustic startle suggest that the effects of PCP in this procedure may represent a model of attentional deficits observed in treatment-resistant schizophrenia.
由先前呈现较低强度刺激所产生的对巨响的惊吓反射幅度降低被称为前脉冲抑制（PPI）。PPI可能会被多种药物破坏，最显著的是多巴胺能激动剂如阿扑吗啡以及苯环利定（PCP）和相关的非竞争性N-甲基-D-天冬氨酸（NMDA）拮抗剂。阿扑吗啡诱导的PPI破坏可被典型和非典型抗精神病药物拮抗。本研究考察了非典型抗精神病药物氯氮平单独以及与PCP联合使用对大鼠PPI的影响。先前研究结果表明，PCP及类似药物对PPI的破坏对典型抗精神病药物如氟哌啶醇的拮抗不敏感。本研究结果表明，氯氮平对PCP诱导的PPI破坏的作用也有限。不同化学类别的临床有效抗精神病药物未能阻断PCP对听觉惊吓PPI的影响，这表明PCP在此过程中的作用可能代表了难治性精神分裂症中观察到的注意力缺陷模型。
