Effects of I-stepholidine on forebrain Fos expression: Comparison with clozapine and haloperidol

doi:10.1038/sj.npp.1300628

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 新药研究国家重点实验室

	Effects of I-stepholidine on forebrain Fos expression: Comparison with clozapine and haloperidol
	Mo, YQ ; Jin, XL ; Chen, YT; Jin, GZ; Shi, WX
刊名	NEUROPSYCHOPHARMACOLOGY
	2005-02
卷号	30 期号:2 页码:261-267
关键词	stepholidine c-fos atypical antipsychotic schizophrenia negative symptoms
ISSN号	0893-133X
DOI	10.1038/sj.npp.1300628
文献子类	Article
英文摘要	l-Stepholidine (SPD) is a tetrahydroprotoberberine alkaloid and a mixed dopamine D1 agonist/D2 antagonist. Preliminary clinical trials suggest that SPD improves both positive and negative symptoms of schizophrenia without producing significant extrapyramidal side effects. Here, we report that SPD mimics the effect of the atypical antipsychotic drug clozapine, preferentially increasing Fos expression in corticolimbic areas. Thus, at 10 mg/kg (i.p.), SPD induced Fos expression in the medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and lateral septal nucleus (LSN) without significantly affecting the dorsolateral striatum (DLSt). At higher doses ( 20 - 40 mg/kg), SPD also increased Fos expression in the DLSt. The increase, however, was less pronounced than the increase seen in the NAc. Within the NAc, SPD also induced more Fos expression in the shell than in the core. In all subcortical areas examined, the Fos expression induced by SPD was mimicked by the D2 antagonist sulpiride and reversed by the D2 agonist quinpirole, suggesting that the effect is due to blockade of D2-like receptors by SPD. In the mPFC, however, the effect was not mimicked by sulpride or reversed by quinpirole. It was also not mimicked by the D1 agonist SKF38393 or SKF38393 plus sulpride, and not reversed by the D1 antagonist SCH23390. These results suggest that, in the mPFC, SPD may induce Fos expression through a non-DA mechanism. Whether the mechanism involves an interaction of SPD with other neurotransmitters such as 5-HT and norepinephrine remains to be determined.
WOS关键词	DOPAMINE RECEPTOR ANTAGONISTS ; MESSENGER-RNA EXPRESSION ; EARLY GENE-EXPRESSION ; ANTIPSYCHOTIC-DRUGS ; NEUROLEPTIC DRUGS ; PREFRONTAL CORTEX ; LESIONED RATS ; (-)-STEPHOLIDINE ; STRIATUM ; BRAIN
WOS研究方向	Neurosciences & Neurology ; Pharmacology & Pharmacy ; Psychiatry
语种	英语
出版者	NATURE PUBLISHING GROUP
WOS记录号	WOS:000226569900005
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/273934]
专题	新药研究国家重点实验室中科院受体结构与功能重点实验室
通讯作者	Shi, WX
作者单位	1.Yale Univ, Sch Med, Dept Psychiat, Neuropsychopharmacol Res Unit, New Haven, CT 06511 USA 2.Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Inst Mat Med, State Key Lab Drug Res,Dept Pharmacol, Shanghai, Peoples R China 3.Fudan Univ, Coll Pharm, Dept Pharmacol, Shanghai 200433, Peoples R China 4.Xuzhou Med Coll, Dept Anat, Xuzhou, Peoples R China
推荐引用方式 GB/T 7714	Mo, YQ,Jin, XL,Chen, YT,et al. Effects of I-stepholidine on forebrain Fos expression: Comparison with clozapine and haloperidol[J]. NEUROPSYCHOPHARMACOLOGY,2005,30(2):261-267.
APA	Mo, YQ,Jin, XL,Chen, YT,Jin, GZ,&Shi, WX.(2005).Effects of I-stepholidine on forebrain Fos expression: Comparison with clozapine and haloperidol.NEUROPSYCHOPHARMACOLOGY,30(2),261-267.
MLA	Mo, YQ,et al."Effects of I-stepholidine on forebrain Fos expression: Comparison with clozapine and haloperidol".NEUROPSYCHOPHARMACOLOGY 30.2(2005):261-267.