l-Stepholidine-Induced Excitation of Dopamine Neurons in Rat Ventral Tegmental Area is Associated With Its 5-HT1A Receptor Partial Agonistic Activity
文献类型：期刊论文
| 作者 | Gao, Ming1,2; Chu, Hong-Yuan1,2; Jin, Guo-Zhang1,2 ; Zhang, Zhang-Jin3,4; Wu, Jie5; Zhen, Xue-Chu1,2
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| 刊名 | SYNAPSE
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| 出版日期 | 2011-05 |
| 卷号 | 65期号:5页码:379-387 |
| 关键词 | l-stepholidine dopamine serotonin schizophrenia slow oscillation single unit recording |
| ISSN号 | 0887-4476 |
| DOI | 10.1002/syn.20855 |
| 文献子类 | Article |
| 英文摘要 | Rationale: l-Stepholidine (l-SPD), a tetrahydroprotoberberine alkaloid, possesses a pharmacological profile of a D-1/5-HT1A agonist and a D-2 antagonist. This unique pharmacological profile makes it a promising novel antipsychotic candidate. Preliminary clinical trials and animal experiments suggest that l-SPD improves both positive and negative symptoms of schizophrenia without producing significant extrapyramidal side effects. To further explore the antipsychotic mechanisms of the drug, we studied the effects of l-SPD on the activity of dopamine (DA) neurons in the ventral tegmental area (VTA) using in vivo single-unit recording technique in rats. Result: We found that l-SPD increased VTA DA neurons firing rate and induced slow oscillation in firing pattern. Moreover, l-SPD, not clozapine, reversed d-amphetamine-induced inhibition which induced an excitation of VTA DA neurons. Furthermore, our data indicated that the excitatory effect of l-SPD is associated with its partial agonistic action for the 5-HT1A receptor since the 5-HT1A receptor antagonist WAY100635 could block the l-SPD-induced excitatory effect. However, activation of 5-HT1A receptor alone by specific agonist (+/-)-8-Hydroxy-2-(dipropylamino) tetralin (8-OH-DPAT) was insufficient to elicit excitation of VTA DA neurons, but the excitation of 8-OH-DPAT on VTA DA neurons was elicited in the presence of D-2-like receptors antagonist raclopride. Collectively, these results indicate that l-SPD excited VTA DA neurons requiring its D-2-like receptors antagonistic activity and 5-HT1A receptor agonistic activity. Conclusion: The present data demonstrate that D-2 receptor antagonist/5-HT1A receptor agonistic dual properties modulate dopaminergic transmission in a unique pattern that may underlie the different therapeutic responses between l-SPD and other atypical antipsychotic drugs. Synapse 65:379-387, 2011. (C) 2010 Wiley-Liss, Inc. |
| WOS关键词 | MEDIAL PREFRONTAL CORTEX ; ANTIPSYCHOTIC-DRUG ; NUCLEUS-ACCUMBENS ; FIRING PATTERN ; SCHIZOPHRENIA ; (-)-STEPHOLIDINE ; OSCILLATIONS ; CLOZAPINE ; SEROTONIN ; RELEASE |
| 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] ; Natural Science Foundation of China[30672448] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program''[2009ZX09301-001] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program''[2009ZX09102-023] |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000288079700003 |
| 出版者 | WILEY-BLACKWELL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278552]  |
| 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, Xue-Chu |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Neuropharmacol, Shanghai 201203, Peoples R China; 3.Univ Hong Kong, Sch Chinese Med, Hong Kong, Hong Kong, Peoples R China; 4.Univ Hong Kong, Fac Med, Hong Kong, Hong Kong, Peoples R China; 5.St Josephs Hosp, Div Neurol, Barrow Neurol Inst, Phoenix, AZ 85013 USA |
| 推荐引用方式 GB/T 7714 | Gao, Ming,Chu, Hong-Yuan,Jin, Guo-Zhang,et al. l-Stepholidine-Induced Excitation of Dopamine Neurons in Rat Ventral Tegmental Area is Associated With Its 5-HT1A Receptor Partial Agonistic Activity[J]. SYNAPSE,2011,65(5):379-387. |
| APA | Gao, Ming,Chu, Hong-Yuan,Jin, Guo-Zhang,Zhang, Zhang-Jin,Wu, Jie,&Zhen, Xue-Chu.(2011).l-Stepholidine-Induced Excitation of Dopamine Neurons in Rat Ventral Tegmental Area is Associated With Its 5-HT1A Receptor Partial Agonistic Activity.SYNAPSE,65(5),379-387. |
| MLA | Gao, Ming,et al."l-Stepholidine-Induced Excitation of Dopamine Neurons in Rat Ventral Tegmental Area is Associated With Its 5-HT1A Receptor Partial Agonistic Activity".SYNAPSE 65.5(2011):379-387. |
入库方式： OAI收割
来源：上海药物研究所
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