Maia-de-Oliveira Joao Paulo, Lobão-Soares Bruno, Ramalho Thais, Gavioli Elaine C, Soares Vanessa Paula, Teixeira Leslie, Baker Glen B, Dursun Serdar M, Hallak Jaime E C
Department of Neuroscience and Behavioral Science, University of Sao Paulo (USP) - Ribeirao Preto, SP CEP 14048-900, Brazil; Department of Clinical Medicine, Federal University of Rio Grande do Norte, Natal, RN CEP 59012420, Brazil.
Department of Biophysics and Pharmacology, Federal University of Rio Grande do Norte (UFRN), Natal, RN, CEP 59012420, Brazil.
Schizophr Res. 2015 Mar;162(1-3):211-5. doi: 10.1016/j.schres.2014.12.035. Epub 2015 Jan 10.
Recently, we found a rapid and long-lasting improvement of symptoms in schizophrenic patients on antipsychotics after a single four-hour infusion of sodium nitroprusside (SNP), a nitric oxide (NO) donor with a short half-life. This improvement persisted for up to 4weeks. Because these patients remained on antipsychotics after infusion of SNP was finished, the question arises about whether this improvement was due to SNP itself. We have now investigated whether SNP, alone, can produce preventive antipsychotic effects in rats treated with ketamine (KET). 56 adult rats divided into 7 groups were infused with SNP 4mg/kg, KET 25mg/kg, or saline as follows: group1 - saline, group2 - SNP, group3 - KET, group4 - KET 12h after SNP, group5 - KET 1day after SNP, group6 - KET 2days after SNP, and group7 - KET 1week after SNP. The animals were filmed in an open field arena for 30min and the videos were later analyzed by ANY-Maze software to measure activity and stereotypy. SNP significantly prevented the emergence of hyperactivity induced by KET when it was administered for up to 1week before KET, and prevented the emergence of stereotypies when it was administered for up to 1day before KET. These findings in rats, which have an even faster metabolic rate than humans, suggest that the long-lasting effects observed in our clinical trial with SNP in humans could have been due to SNP itself, and indicate for the first time that SNP may present preventive antipsychotic effects.
最近，我们发现，在对精神分裂症患者单次静脉输注半衰期较短的一氧化氮（NO）供体硝普钠（SNP）4小时后，使用抗精神病药物治疗的患者症状得到了快速且持久的改善。这种改善持续了长达4周。由于在输注SNP结束后这些患者仍继续使用抗精神病药物，因此出现了这种改善是否归因于SNP本身的问题。我们现在研究了单独使用SNP是否能在接受氯胺酮（KET）治疗的大鼠中产生预防性抗精神病作用。将56只成年大鼠分为7组，分别按如下方式输注4mg/kg的SNP、25mg/kg的KET或生理盐水：第1组 - 生理盐水，第2组 - SNP，第3组 - KET，第4组 - 在SNP后12小时给予KET，第5组 - 在SNP后1天给予KET，第6组 - 在SNP后2天给予KET，第7组 - 在SNP后1周给予KET。将动物置于旷场 arena 中拍摄30分钟，随后通过ANY - Maze软件分析视频以测量活动和刻板行为。当在给予KET前长达1周给予SNP时，SNP能显著预防由KET诱导的多动的出现；当在给予KET前长达1天给予SNP时，能预防刻板行为的出现。在代谢率比人类更快的大鼠中的这些发现表明，我们在人类中使用SNP的临床试验中观察到的持久效应可能归因于SNP本身，并首次表明SNP可能具有预防性抗精神病作用。
