Short- and long-term effects of p-ethynylphenylalanine on brain serotonin levels.
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.
Zimmer
Luc
L
CERMEP Biomedical Cyclotron, Lyon, France. zimmer@cermep.fr
Luxen
André
A
Giacomelli
Fabrice
F
Pujol
Jean-François
JF
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013997:Time Factors; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors*
C408243:p-ethynylphenylalanine; D012701:Serotonin; D014365:Tryptophan Hydroxylase; D000409:Alanine