Bergqvist P B, Hjorth S, Wikell C, Apelqvist G, Bengtsson F
Department of Clinical Pharmacology, Institute of Laboratory Medicine, Lund University, Sweden.
Metab Brain Dis. 1997 Sep;12(3):229-36.
Portal-systemic encephalopathy (PSE) is associated with increased brain turnover of serotonin (5-HT) in vivo but the brain 5-HT output seems to be unaltered. Recent results suggest, however, that an augmented neocortical 5-HT release in experimental chronic PSE may prevail under certain conditions. In the present study, neocortical extracellular 5-HT and 5-hydroxyindoleacetic-3-acid (5-HIAA) levels were measured in portacaval shunted (PCS) rats and sham-operated controls following local administration of p-chloroamphetamine (pCA) and d-fenfluramine (dFEN), two specific 5-HT releasing agents. The basal neocortical extracellular 5-HT concentrations were unaltered and the 5-HIAA levels were elevated in experimental PSE, supporting an unchanged brain 5-HT output despite elevated brain 5-HT metabolism. Perfusion with pCA or dFEN (5 microM; one 20-min pulse) produced marked increases in brain 5-HT release both in PCS and sham-operated rats compared with corresponding basal values. While no difference in the 5-HT response to dFEN administration was seen between sham (5-HT levels increased by 330%) and PCS (500%) rats, a clear difference (p<0.05) in the brain 5-HT output was observed between the two experimental groups following pCA perfusion (sham, 1100% versus PCS, 1470%). These results support our previous contention of an enhanced neocortical 5-HT output in experimental chronic PSE under certain pharmacological conditions.
门体分流性脑病（PSE）与体内血清素（5-羟色胺，5-HT）的脑更新增加有关，但脑5-HT输出似乎未改变。然而，最近的结果表明，在某些条件下，实验性慢性PSE中新皮质5-HT释放增加可能占主导。在本研究中，在对门腔分流（PCS）大鼠和假手术对照组局部给予对氯苯丙胺（pCA）和右旋芬氟拉明（dFEN）这两种特定的5-HT释放剂后，测量了新皮质细胞外5-HT和5-羟吲哚乙酸-3-酸（5-HIAA）水平。实验性PSE中，基础新皮质细胞外5-HT浓度未改变，5-HIAA水平升高，这支持了尽管脑5-HT代谢升高，但脑5-HT输出未改变的观点。与相应的基础值相比，用pCA或dFEN（5微摩尔；一个20分钟脉冲）灌注后，PCS大鼠和假手术大鼠的脑5-HT释放均显著增加。虽然在假手术（5-HT水平增加330%）和PCS（500%）大鼠之间，对dFEN给药的5-HT反应没有差异，但在pCA灌注后，两个实验组之间观察到脑5-HT输出有明显差异（p<0.05）（假手术组为1100%，PCS组为1470%）。这些结果支持了我们之前的观点，即在某些药理学条件下，实验性慢性PSE中新皮质5-HT输出增强。
