Henan Mental Hospital, The Second Affiliated Hospital of Xinxiang Medical University, No.388, Jianshe Middle Road, Xinxiang, 453002, Henan, People's Republic of China.
Wuhan Mental Health Center, The Ninth Clinical College of Huazhong University of Science and Technology, No.93, Youyi Road, Wuhan, 430022, Hubei, People's Republic of China.
Brain Res Bull. 2019 Apr;147:140-147. doi: 10.1016/j.brainresbull.2019.02.008. Epub 2019 Feb 14.
Schizophrenia treatment remains a major challenge, especially the associated cognitive impairments, as these are not consistently alleviated by conventional antipsychotics. Recent animal and clinical studies suggest that the nitric oxide (NO) donor sodium nitroprusside (SNP) reduces the psychiatric symptoms and cognitive deficits of schizophrenia. The present study was designed to investigate the efficacy of SNP against schizophrenia-like behavioral and cognitive deficits in the dizocilpine (MK-801) rat model. We used the rotarod and open field tests to identify the SNP dose which had no adverse effects on rat's exploratory and motor behavior, then established the schizophrenia model by injecting adult Sprague-Dawley rats intraperitoneally with MK-801 (0.4 mg/kg) with or without SNP pre-treatment. Behavioral changes were examined after 10 min. Prepulse inhibition (PPI) and the Y maze tests were conducted to assess cognitive deficits, and elevated plus maze and open field tests to assess anxiety-like behaviors. Preliminary rotarod and open field tests demonstrated that 2.5 mg/kg SNP had no effect on motor performance. Acute MK-801 treatment induced both cognitive deficits and anxiety. Co-administration of SNP (2.5 mg/kg) failed to improve these schizophrenia-like abnormalities. Sodium nitroprusside appears unable to improve schizophrenia-like symptoms and cognitive deficits induced by MK-801, inconsistent with the effectiveness of SNP as an adjunct therapy for anxiety disorders and working memory impairments in schizophrenia patients. Future studies are required to define an effective dose range for SNP monotherapy and adjunct therapy in different rodent models.
精神分裂症的治疗仍然是一个主要的挑战，特别是相关的认知障碍，因为这些障碍并没有被传统的抗精神病药物持续缓解。最近的动物和临床研究表明，一氧化氮（NO）供体硝普钠（SNP）可以减轻精神分裂症的精神症状和认知缺陷。本研究旨在研究 SNP 对二氮嗪（MK-801）诱导的精神分裂样行为和认知缺陷的疗效。我们使用转棒和旷场试验来确定 SNP 的剂量，该剂量对大鼠的探索和运动行为没有不良影响，然后通过腹腔注射 MK-801（0.4mg/kg）建立精神分裂症模型，同时或不预先给予 SNP。在 10 分钟后检查行为变化。进行条件性惊吓反射（PPI）和 Y 迷宫测试以评估认知缺陷，以及高架十字迷宫和旷场测试以评估焦虑样行为。初步的转棒和旷场试验表明，2.5mg/kg SNP 对运动表现没有影响。急性 MK-801 治疗引起认知缺陷和焦虑。SNP（2.5mg/kg）的联合给药未能改善这些精神分裂样异常。硝普钠似乎无法改善 MK-801 诱导的精神分裂样症状和认知缺陷，与 SNP 作为焦虑障碍和精神分裂症患者工作记忆障碍的辅助治疗的有效性不一致。需要进一步的研究来确定 SNP 单药治疗和辅助治疗在不同啮齿动物模型中的有效剂量范围。
