p-chlorophenylalanine increases tryptophan-5-hydroxylase mRNA levels in the rat dorsal raphe: a time course study using in situ hybridization.
The effects of a single dose of p-chlorophenylalanine on the mRNA encoding tryptophan-5-hydroxylase (EC 1.14.16.4) in the rat dorsal raphe nucleus were analyzed using in situ hybridization. The levels of tryptophan-5-hydroxylase mRNA were markedly increased in cell bodies located in the ventromedial part of the dorsal raphe 1-2 days after p-chlorophenylalanine (300 mg/kg, i.p.) administration. This was followed by a decrease in the amount of tryptophan-5-hydroxylase mRNA, which returned to basal values by 5 days after treatment. An almost symmetric time course was observed for the midbrain serotonin concentration. Our results on the temporal pattern of changes in tryptophan-5-hydroxylase mRNA levels in the ventromedial part of the dorsal raphe are opposite to those reported for the enzyme activity and serotonin concentration after p-chlorophenylalanine treatment. These changes may result from modifications in enzyme mRNA expression, suggesting that tryptophan-5-hydroxylase gene transcription is involved in feedback mechanisms regulating serotonin synthesis.
Cortés
R
R
Department of Neurochemistry, C.I.D.-C.S.I.C., Barcelona, Spain.
Mengod
G
G
Celada
P
P
Artigas
F
F
D000818:Animals; D015152:Blotting, Northern; D010134:Fenclonine / Q000494:pharmacology*; D017403:In Situ Hybridization; D007700:Kinetics; D008297:Male; D015345:Oligonucleotide Probes; D012333:RNA, Messenger / Q000378:metabolism*; D011903:Raphe Nuclei / Q000187:drug effects / Q000201:enzymology*; D051381:Rats; D013997:Time Factors; D014365:Tryptophan Hydroxylase / Q000235:genetics*
D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D014365:Tryptophan Hydroxylase; D010134:Fenclonine