Effects of sodium nitroprusside in the prevention of schizophrenia-like symptoms induced by ketamine – A translational double-blind study

Abstract Background: Recent evidence has shown improvements in schizophrenia symptoms after the infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor. In the rat model of schizophrenia using ketamine injection, pretreatment with SNP seems to prevent behavioral changes associated with positive symptoms for up to one week. Objective: We investigated whether SNP would have preventative effects on psychogenic symptoms induced by ketamine in healthy subjects. Methods: Healthy subjects (N = 38) were assigned to distinct groups that received SNP in different doses (0.15, 0.25, and 0.5 mcg/kg/min). First, participants received an infusion of SNP or placebo over 75 minutes. After 10 minutes, they were injected for 1 minute with a bolus of 0.26 mg/kg of ketamine and a maintenance dose was started 5 minutes later, with 0.25 mg/kg/h of ketamine for 50 minutes. Results: Ketamine-induced psychopathological alterations induced were reduced by SNP, as assessed with the Brief Psychological Rating Scale. Scores in the objective subscale of the Clinician-Administered Dissociative States Scale were also lower in SNP sessions compared to placebo. SNP had protective effects against deterioration in facial emotion and identity recognition tasks induced by ketamine. Discussion: Our findings support the view that SNP has preventative properties against psychotic manifestations.

背景：近期研究证实，一氧化氮（nitric oxide, NO）供体硝普钠（sodium nitroprusside, SNP）静脉输注可改善精神分裂症患者的症状。在氯胺酮（ketamine）注射诱导的精神分裂症大鼠模型中，硝普钠预处理可预防与阳性症状相关的行为改变，且该保护作用可持续长达一周。
目的：本研究旨在探讨硝普钠对健康受试者氯胺酮诱导的精神病性症状是否具有预防作用。
方法：共纳入38名健康受试者，按不同给药剂量（0.15、0.25、0.5 mcg/kg/min）分为多个组别。受试者首先接受75分钟的硝普钠或安慰剂静脉输注；输注10分钟后，以0.26 mg/kg的剂量推注氯胺酮1分钟，5分钟后启动维持给药方案：以0.25 mg/kg/h的速率输注氯胺酮，持续50分钟。
结果：采用简明心理评定量表（Brief Psychological Rating Scale）评估显示，硝普钠可减轻氯胺酮诱导的精神病理改变。与安慰剂组相比，硝普钠给药组在临床医师评定分离状态量表（Clinician-Administered Dissociative States Scale）的客观子量表中得分更低。此外，硝普钠可保护受试者免受氯胺酮诱导的面部情绪与身份识别任务表现恶化。
讨论：本研究结果支持硝普钠对精神病性表现具有预防作用这一观点。