Evaluation of the antipsychotic effect of bi-acetylated l-stepholidine (l-SPD-A), a novel dopamine and serotonin receptor dual ligand
文献类型：期刊论文
| 作者 | Guo, Yang; Zhang, Hai; Chen, Xuetao; Cai, Wenxian; Cheng, Jianjun; Yang, Yushe ; Jin, Guozhang; Zhen, Xuechu
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| 刊名 | SCHIZOPHRENIA RESEARCH
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| 出版日期 | 2009-11 |
| 卷号 | 115期号:1页码:41-49 |
| 关键词 | Bi-acetylated l-stepholidine (l-SPD-A) Phencyclidine (PCP) Schizophrenia Behavior Dopamine D-1 receptor |
| ISSN号 | 0920-9964 |
| DOI | 10.1016/j.schres.2009.08.002 |
| 文献子类 | Article |
| 英文摘要 | Bi-acetylated l-stepholidine (l-SPD-A), a novel derivate of l-stepholidine (l-SPD), possesses a pharmacological profile of D-1/5-HT1A agonism and D-2 antagonism. In the present study, we examined the potential antipsychotic effect of l-SPD-A in a phencyclidine (PCP)-induced rat model of schizophrenia. Pretreatment with l-SPD-A blocked acute PCP-induced hyperlocomotion and reversed prepulse inhibition (PPI) deficits. Chronic l-SPD-A administration (i.p., 10 mg/kg/day for 14 days) improved social interaction and novel object recognition impairments in rats that were pretreated with PCP (i.p., 5 mg/kg/day for 14 days). Moreover, in a conditioned avoidance response (CAR) test, l-SPD-A, with either i.p. or oral administration, significantly decreased active avoidance without affecting the escape response of rats. Importantly, compared to that of the parent compound l-SPD, l-SPD-A showed stronger suppression of CARS. Lastly, using a [S-35]GTP-gamma S binding assay, we demonstrated that l-SPD-A improved impaired dopamine D-1 receptor function in the prefrontal cortex (PFC) in chronic PCP-treated rats. Taken together, these results indicate that l-SPD-A was not only effective against the hyperactivity, but also improved the sensorimotor gating deficit, social withdrawal and cognitive impairment in an animal model of schizophrenia. The present data suggest that l-SPD-A, a potential neurotransmitter stabilizer, is a promising novel candidate drug for the treatment of schizophrenia. (C) 2009 Elsevier B.V. All rights reserved. |
| WOS关键词 | SOCIAL-INTERACTION DEFICITS ; ROTATIONAL BEHAVIOR ; PREFRONTAL CORTEX ; 5-HT1A RECEPTORS ; WORKING-MEMORY ; D-1 RECEPTOR ; RAT-BRAIN ; SCHIZOPHRENIA ; AGONIST ; D1 |
| 资助项目 | Ministry of Science and Technology of China[2007AA02z163] ; Ministry of Science and Technology of China[2009CB522201] ; Natural Science Foundation of China[30770662] ; Natural Science Foundation of China[30825042] |
| WOS研究方向 | Psychiatry |
| 语种 | 英语 |
| WOS记录号 | WOS:000271686400007 |
| 出版者 | ELSEVIER SCIENCE BV |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/279097]  |
| 专题 | 药理学第二研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Zhen, Xuechu |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Dept Neuropharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Guo, Yang,Zhang, Hai,Chen, Xuetao,et al. Evaluation of the antipsychotic effect of bi-acetylated l-stepholidine (l-SPD-A), a novel dopamine and serotonin receptor dual ligand[J]. SCHIZOPHRENIA RESEARCH,2009,115(1):41-49. |
| APA | Guo, Yang.,Zhang, Hai.,Chen, Xuetao.,Cai, Wenxian.,Cheng, Jianjun.,...&Zhen, Xuechu.(2009).Evaluation of the antipsychotic effect of bi-acetylated l-stepholidine (l-SPD-A), a novel dopamine and serotonin receptor dual ligand.SCHIZOPHRENIA RESEARCH,115(1),41-49. |
| MLA | Guo, Yang,et al."Evaluation of the antipsychotic effect of bi-acetylated l-stepholidine (l-SPD-A), a novel dopamine and serotonin receptor dual ligand".SCHIZOPHRENIA RESEARCH 115.1(2009):41-49. |
入库方式： OAI收割
来源：上海药物研究所
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