Modulation of dopamine release by striatal 5-HT2C receptors
Modulation of dopamine release by striatal 5-HT2C receptors
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DOI：
10.1002/syn.20109
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发表时间：
2005-03-15
期刊：
影响因子：
2.3
通讯作者：
Pehek, EA
中科院分区：
文献类型：
--
作者：
Alex, KD;Yavanian, GJ;Pehek, EA
以往的工作表明，多巴胺(DA)的传递受5-羟色胺-2C(5-1-17172C)受体的调节，但这些受体在大脑中的定位位置(S)尚不清楚。本工作利用体内微透析技术，研究了位于中皮质和黑质纹状体DA通路神经末梢区域的5-HT2C受体对DA释放的调节作用。植入纹状体或前额叶皮质的微透析探针测量透析液中DA的浓度，而选择性的5-HT2B/2C反向激动剂SB 206553则通过反向透析进入这些终末区域。此外，还测定了5-HT2C激动剂mCPP对纹状体DA的影响。纹状体内局部注射SB 206553(0.1um~100um)可浓度依赖性地增加DA外流。MCPP(1.0 mg/kg ip)全身给药降低纹状体DA，减弱SB-206553所致的升高。相反，向前额叶内注入SB 206553(0.1um~500um)对该区域的基础DA外流无明显影响。此外，高浓度Sb 206553对高钾(K+)刺激的前额叶细胞DA释放无影响。这些数据为5-HT2C受体抑制黑质纹状体多巴胺能传递提供了大量证据。此外，结果表明黑质纹状体系统受位于背侧纹状体的5-HT2C受体的调节。阐明5-羟色胺(5-HT)调节纹状体和前额叶皮质DA浓度的机制可能会改善对各种综合征的治疗，如精神分裂症、帕金森病、焦虑、药物滥用和/或抑郁症。2005年出版，Wiley-Liss，lnc(匕首)。
Previous work has demonstrated that dopamine (DA) transmission is regulated by serotonin-2C (5-1-17172C) receptors but the site(s) in the brain where these receptors are localized is not known. The present work utilized in vivo microdialysis to investigate the modulation of DA release by 5-HT2C receptors localized in the nerve terminal regions of the mesocortical and nigrostriatal DA pathways. Microdialysis probes implanted in the striatum or the prefrontal cortex (PFC) measured dialysate DA concentrations, while the selective 5-HT2B/2C inverse agonist SB 206553 was given locally by reverse dialysis into these terminal regions. Additionally, the effects of the 5-HT2C agonist mCPP on striatal DA were measured. Local administration of SB 206553 (0.1-100 muM) into the striatum increased DA efflux in a concentration-dependent manner. Systemic administration of mCPP (1.0 mg/kg i.p.) decreased striatal DA and attenuated the SB 206553-induced increase. In contrast, infusion of SB 206553 (0.1-500 muM) by reverse dialysis into the PFC had no significant effect on basal DA efflux in this region. Additionally, high concentrations of SB 206553 had no effect on high potassium (K+)-stimulated DA release in the PFC. These data contribute to a body of evidence indicating that 5-HT2C receptors inhibit nigrostriatal dopaminergic transmission. In addition, the results suggest that the nigrostriatal system is regulated by 5-HT2C receptors localized in the dorsal striatum. Elucidating the mechanisms by which serotonin (5-HT) modulates striatal and prefrontocortical DA concentrations may lead to improvements in the treatment of diverse syndromes such as schizophrenia, Parkinson's disease, anxiety, drug abuse, and/or depression. Published 2005 Wiley-Liss, lnc(dagger).