Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Thessaly, Larissa, Greece.
Department of Pharmacology, School of Medicine, Faculty of Health Sciences, University of Thessaly, Larissa, Greece.
Nitric Oxide. 2017 Sep 30;69:56-60. doi: 10.1016/j.niox.2017.05.002. Epub 2017 May 15.
The nitric oxide (NO) donor sodium nitroprusside (SNP) actually is under investigation for the treatment of schizophrenia. That anxiety disorders are noted to occur commonly in schizophrenia patients is known. Contradictory results were reported however, concerning the effects of SNP in animal models of anxiety disorders. The present study investigated the effects of acute and repeated administration of SNP on anxiety-like behaviour in rats assessed in the light/dark test. The effects of SNP on motility in a locomotor activity chamber were also investigated in rats. Acute administration of 1 mg/kg SNP 30 but not 60 min before testing induced anxiolytic-like behaviour which cannot be attributed to changes in locomotor activity. Conversely, a single injection of 3 mg/kg SNP at 30 min before testing depressed rats' general activity, while at 60 min this dose did not influence performance of animals either in the light/dark or in the motor activity test. Repeated application of SNP (1 and 3 mg/kg, for 5 consecutive days) did not alter rodents' performance in the above described behavioural paradigms. The present results suggest that the effects exerted by SNP in the light/dark test in rats are dose, time and treatment schedule-dependent. The current findings propose also a narrow therapeutic window for SNP in this animal model of anxiety.
一氧化氮（NO）供体硝普钠（SNP）实际上正在被研究用于治疗精神分裂症。众所周知，焦虑障碍在精神分裂症患者中经常发生。然而，关于 SNP 在焦虑障碍动物模型中的作用，报告的结果却相互矛盾。本研究在明暗箱测试中，研究了 SNP 在急性和重复给药后对大鼠焦虑样行为的影响。还研究了 SNP 对大鼠在运动活动室中运动的影响。急性给予 SNP（1 mg/kg），在测试前 30 分钟但不是 60 分钟给药，诱导出具有抗焦虑作用的行为，这不能归因于运动活性的变化。相反，单次注射 SNP（3 mg/kg）在测试前 30 分钟会抑制大鼠的一般活动，而在 60 分钟时，该剂量既不影响动物在明暗箱或运动活性测试中的表现。SNP（1 和 3 mg/kg，连续 5 天）的重复应用并未改变啮齿动物在上述行为范式中的表现。目前的结果表明，SNP 在大鼠明暗箱测试中的作用取决于剂量、时间和治疗方案。目前的研究结果还提出了 SNP 在这种焦虑动物模型中的治疗窗狭窄。
