Short- and long-term effects of p-ethynylphenylalanine on brain serotonin levels

[en] 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.

Research Center/Unit :

GIGA CRC (Cyclotron Research Center) In vivo Imaging-Aging & Memory - ULiège

Disciplines :

Life sciences: Multidisciplinary, general & others

Author, co-author :

Zimmer, Luc; CERMEP

Luxen, André ; Université de Liège - ULiège > Département de chimie (sciences) > Chimie organique de synthèse - Centre de recherches du cyclotron

Giacomelli, Fabrice ; Université de Liège - ULiège > Centre de recherches du cyclotron

Pujol, Jean-François

Language :

English

Title :

Short- and long-term effects of p-ethynylphenylalanine on brain serotonin levels

Publication date :

April 2002

Journal title :

Neurochemical Research

ISSN :

0364-3190

eISSN :

1573-6903

Publisher :

Kluwer Academic/Plenum Publ, New York, United States - New York

Volume :

Issue :

Pages :

269-275

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

http://www.springerlink.com/content/lk1jl16qfax66nbe/

Available on ORBi :

since 26 October 2010

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Bibliography

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