Short- and Long-Term Effects of p-Ethynylphenylalanine on Brain Serotonin Levels

被引：0
作者：
Luc Zimmer
André Luxen
Fabrice Giacomelli
Jean-François Pujol
机构：
[1] CERMEP Biomedical Cyclotron,Cyclotron Research Center
[2] INSERM U512,undefined
[3] Liège University,undefined
来源：
Neurochemical Research | 2002年 / 27卷
关键词：
Tryptophan hydroxylase; p-ethynylphenylalanine; serotonin synthesis; catecholamines; microdialysis;
D O I：
暂无
中图分类号：
学科分类号：
摘要：
Changes in tissue and extracellular serotonin (5-HT) in raphe dorsalis, raphe medialis and in their main projections areas (hippocampus, striatum and frontal cortex) were investigated at short and long-term times after single injection (5 mg/kg ip) of a novel tryptophan hydroxylase inhibitor, p-ethynylphenylalanine (p-EPA). The 5-HT tissue concentration decreased significantly in raphe nuclei, 30 min post-injection and for 4 days, whereas it decreased from 24 hours post-injection in the 5-HT projections. Normal 5-HT levels reappeared after 12 days post-injection in all areas. Moreover, in the projection areas, the extracellular 5-HT levels decreased rapidly, 90, 40 and 30 min after p-EPA injection, in hippocampus, striatum and frontal cortex, respectively. Decreased accumulation of 5-hydroxytryptophan (5-HTP) under NSD-101 perfusion in the serotoninergic projections after p-EPA injection, confirmed the direct inhibitory effect of the drug on the tryptophan hydroxylase activity. These results demonstrated that p-EPA is a useful pharmacological tool which powerfully, acutely and irreversibly reduces the 5-HT levels.
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收藏
页码：269 / 275
页数：6
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