Kreiss D S, Wieland S, Lucki I
Institute of Neurological Sciences, University of Pennsylvania, Philadelphia 19104.
Neuroscience. 1993 Jan;52(2):295-301. doi: 10.1016/0306-4522(93)90157-b.
The present study investigated the effects of the presence of the serotonin uptake inhibitor citalopram in the perfusion medium on pharmacological manipulations which increased and decreased striatal serotonin release using in vivo microdialysis. A high performance liquid chromatography detection system equipped with a microbore column was used which reduced the detection limit to 0.5 fmol serotonin/5 microliters sample and enabled basal striatal serotonin release to be measured without the addition of a serotonin uptake inhibitor to the perfusion medium. Although serotonin uptake inhibitors have frequently been used to enhance the serotonin content of dialysate samples, the effects of the presence of serotonin uptake inhibitors on pharmacological manipulations which increased and decreased the release of serotonin have not yet been characterized. Serotonin release was reduced by the systemic administration of the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Although 5-HT release was reduced by 8-OH-DPAT after the addition of citalopram, the 5-HT1A receptor agonist did not reduce absolute levels of extracellular serotonin below basal values of serotonin measured in the absence of citalopram. In addition, citalopram dramatically prevented the four-fold increase in the release of serotonin produced by the systemic administration of the serotonin-releasing agent fenfluramine. The blockade of fenfluramine's effects by citalopram supports the hypothesis that transport of fenfluramine into serotonergic neurons is necessary to increase serotonin release. This study demonstrates that the use of an HPLC detection system equipped with a microbore column can reliably measure basal serotonin release using in vivo microdialysis.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究使用体内微透析技术，调查了灌注介质中血清素摄取抑制剂西酞普兰的存在对增加和减少纹状体血清素释放的药理学操作的影响。使用了配备微径柱的高效液相色谱检测系统，该系统将检测限降低至0.5飞摩尔血清素/5微升样品，并能够在不向灌注介质中添加血清素摄取抑制剂的情况下测量纹状体基础血清素释放。尽管血清素摄取抑制剂经常被用于提高透析液样品中的血清素含量，但血清素摄取抑制剂的存在对增加和减少血清素释放的药理学操作的影响尚未得到描述。全身给予5-HT1A受体激动剂8-羟基-2-(二正丙基氨基)四氢萘(8-OH-DPAT)可降低血清素释放。虽然添加西酞普兰后8-OH-DPAT可降低5-HT释放，但5-HT1A受体激动剂并未使细胞外血清素的绝对水平降至在无西酞普兰情况下测得的血清素基础值以下。此外，西酞普兰显著阻止了血清素释放剂芬氟拉明全身给药所产生的血清素释放四倍增加。西酞普兰对芬氟拉明作用的阻断支持了这样一种假说，即芬氟拉明转运到血清素能神经元中对于增加血清素释放是必要的。本研究表明，使用配备微径柱的HPLC检测系统可以通过体内微透析可靠地测量基础血清素释放。(摘要截短至250字)
