Yan Q S
Department of Biochemical and Therapeutic Sciences, University of Illinois College of Medicine, Peoria 61656, USA.
Brain Res Bull. 2000 Jan 1;51(1):75-81. doi: 10.1016/s0361-9230(99)00208-7.
This study was designed to assess the involvement of the 5-hydroxytryptamine (5-HT)2A/2C receptor subtypes in the regulation of in vivo dopamine release in the rat nucleus accumbens (NAC). Extracellular dopamine (DA) in the NAC was measured using intracerebral microdialysis coupled with an HPLC-EC system. 5-HT2A/2C receptor agonist, (+/-)-1-(4-lodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI) and antagonists, LY-53,857 and ketanserin, were all administered via a dialysis probe into the NAC. The results showed that perfusion with DOI at concentrations of 10, 50, 100, and 300 microM elicited a significant and concentration-dependent increase in extracellular DA. DA levels returned to control values within 40-60 min after terminating DOI perfusion. The increased DA induced by perfusion with 100 microM DOI was sensitive to sodium channel blockade with tetrodotoxin, and antagonized by co-perfusion with either LY-53,857 (25 and 50 microM) or ketanserin (50 microM). Perfusion with 50 microM LY-53,857 alone failed to alter basal levels of DA. The results suggest that local application of DOI increases DA release via a receptor-mediated process, and are consistent with the concept that activation of 5-HT2A/2C receptors within the NAC can augment dopaminergic transmission in this region although these receptors are not involved in the regulation of basal accumbal DA release.
本研究旨在评估5-羟色胺（5-HT）2A/2C受体亚型在调节大鼠伏隔核（NAC）体内多巴胺释放中的作用。采用脑内微透析结合高效液相色谱-电化学检测系统（HPLC-EC）测量NAC中的细胞外多巴胺（DA）。5-HT2A/2C受体激动剂（±）-1-（4-碘-2,5-二甲氧基苯基）-2-氨基丙烷（DOI）以及拮抗剂LY-53,857和酮色林均通过透析探针注入NAC。结果显示，用浓度为10、50、100和300微摩尔的DOI灌注可引起细胞外DA显著且呈浓度依赖性增加。终止DOI灌注后40 - 60分钟内，DA水平恢复至对照值。用100微摩尔DOI灌注诱导的DA增加对河豚毒素所致的钠通道阻断敏感，并被与LY-53,857（25和50微摩尔）或酮色林（50微摩尔）共同灌注所拮抗。单独用50微摩尔LY-53,857灌注未能改变DA的基础水平。结果表明，局部应用DOI通过受体介导的过程增加DA释放，这与以下概念一致：尽管这些受体不参与伏隔核基础DA释放的调节，但激活NAC内的5-HT2A/2C受体可增强该区域的多巴胺能传递。
