Evaluation of the antipsychotic effect of bi-acetylated l-stepholidine (l-SPD-A), a novel dopamine and serotonin receptor dual ligand

doi:10.1016/j.schres.2009.08.002

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	Evaluation of the antipsychotic effect of bi-acetylated l-stepholidine (l-SPD-A), a novel dopamine and serotonin receptor dual ligand
	Guo, Yang; Zhang, Hai; Chen, Xuetao; Cai, Wenxian; Cheng, Jianjun; Yang, Yushe; Jin, Guozhang; Zhen, Xuechu
刊名	SCHIZOPHRENIA RESEARCH
	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.
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关键词	SOCIAL-INTERACTION DEFICITS ; ROTATIONAL BEHAVIOR ; PREFRONTAL CORTEX ; 5-HT1A RECEPTORS ; WORKING-MEMORY ; D-1 RECEPTOR ; RAT-BRAIN ; SCHIZOPHRENIA ; AGONIST ; D1
WOS研究方向	Psychiatry
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000271686400007
内容类型	期刊论文
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.