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.

研究背景：现有研究证据表明，一氧化氮（nitric oxide, NO）供体硝普钠（sodium nitroprusside, SNP）输注治疗可改善精神分裂症患者的临床症状。在氯胺酮（ketamine）诱导的精神分裂症大鼠模型中，经硝普钠预处理可预防与阳性症状相关的行为改变，该保护效应可持续长达一周。
研究目的：本研究旨在探究硝普钠对健康受试者氯胺酮诱导的精神性症状是否具有预防效果。
研究方法：共纳入38名健康受试者，将其分配至不同组别，分别接受剂量为0.15、0.25及0.5 mcg/kg/min的硝普钠输注。首先，受试者接受时长75分钟的硝普钠或安慰剂输注；10分钟后，以0.26 mg/kg的剂量行1分钟氯胺酮弹丸式推注，并于5分钟后启动维持给药方案，以0.25 mg/kg/h的速率持续输注氯胺酮50分钟。
研究结果：经简明心理评定量表（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，硝普钠干预组在医师评定分离状态量表（Clinician-Administered Dissociative States Scale）的客观分量表得分亦显著更低。此外，硝普钠可保护受试者免受氯胺酮诱导的面部情绪识别与身份识别任务表现受损。
研究讨论：本研究结果支持硝普钠对精神病性表现具有预防作用的学术观点。