摘要
目的研究左旋金黄紫堇碱(l-SLR)的抗精神分裂症作用。方法采用NMDA受体拮抗剂MK-801在动物模型上诱发精神分裂症的阳性症状、阴性症状及认知损伤;评价了化合物l-SLR对MK-801诱发的精神分裂症的作用;并评价了l-SLR对小鼠锥体外系功能的影响。结果 MK-801(0.3 mg·kg-1,ip)引起大鼠前脉冲抑制损伤,l-SLR(10、15mg·kg-1,ip)能抑制MK-801引起的大鼠前脉冲抑制损伤;l-SLR(30 mg·kg-1,ip)能抑制多巴胺受体激动剂阿扑吗啡(2 mg·kg-1,sc)引起小鼠的攀爬行为,说明l-LSR对MK-801及阿扑吗啡诱发的精神分裂症阳性症状有抑制作用。lSLR(30 mg·kg-1,ip)能抑制MK-801(0.2 mg·kg-1,ip)引起的小鼠群居接触抑制及MK-801诱发的小鼠认知损伤,说明l-SLR能改善MK-801诱发的精神分裂症阴性症状和认知障碍。经典抗精神分裂药氟哌啶醇在治疗剂量下(0.8 mg·kg-1,ip)诱发小鼠木僵行为,l-SLR在抗精神分裂的剂量下(30 mg·kg-1,ip)不会诱发木僵行为。结论化合物lSLR对精神分裂症的阳性症状、阴性症状以及认知障碍均有效,而且其在有效剂量时对锥体外系的影响明显小于氟哌啶醇和l-SPD。
Aim To study the antipsychotic effects of l-Scoulerine( l-SLR). Methods NMDA receptor antag-onist MK-801 was used to induce the positive and negative symptoms of schizophrenia and cognitive impairment in animal models. The effects of l-SLR were evaluated on schizophrenia induced by MK-801 and on extrapyramidal system. Results l-SLR( 10,15 mg ·kg- 1,ip) could suppress pre-pulse inhibition damage in rats induced by MK-801( 0. 3 mg · kg- 1,ip); lSLR( 30 mg·kg- 1,ip) could inhibit climbing behaviors in mice induced by apomorphine,which suggested that l-SLR had significant inhibiting effects on the positive symptoms of schizophrenia by MK-801 and apomorphine. l-SLR could also induce social contact inhibition and cognitive impairment induced by MK-801( 0. 2 mg · kg- 1,ip),which proposed that l-SLR could improve the negative symptoms and cognitive impairment by MK-801. Catalepsy in mice could be caused by the treatment dose of haloperidol( 0. 8 mg·kg- 1,ip),not by that of l-SLR( 30 mg·kg- 1,ip).Conclusion I-SLR has significant effects on the positive and negative symptoms of schizophrenia and cognitive impairment and,the effect of l-SLR under effective dose on extrapyramidal system is obviously much less than that of haloperidol and l-SPD.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2016年第1期103-109,共7页
Chinese Pharmacological Bulletin
基金
国家自然科学基金面上项目(No 81473193)
军队"十二五"重大专项课题(No 2012ZX09031)
