Chronic D-fenfluramine decreases serotonin transporter messenger RNA expression in dorsal raphe nucleus.
In situ hybridization was used to measure the effects of chronic fenfluramine administration on serotonin transporter messenger RNA expression in cells of the dorsal raphe nucleus complex. Fenfluramine produced a significant, but transient, down-regulation of serotonin transporter mRNA in cells which lie in the ventral portion of the dorsal raphe nucleus, but not in the dorsal part of the dorsal raphe nucleus. Our findings suggest that cells which lie in the ventral part of the dorsal raphe nucleus are more sensitive to the effects of chronic fenfluramine administration, but that fenfluramine does not cause long-term changes in gene expression in serotonin cell bodies.
Rattray
M
M
Molecular Neuropharmacology Laboratory, UMDS Division of Biochemistry, University of London, Guy's Hospital, UK.
Wotherspoon
G
G
Savery
D
D
Baldessari
S
S
Marden
C
C
Priestley
J V
JV
Bendotti
C
C
D000818:Animals; D001483:Base Sequence; D002352:Carrier Proteins / Q000096:biosynthesis*; D003864:Depression, Chemical; D015536:Down-Regulation / Q000187:drug effects; D005277:Fenfluramine / Q000494:pharmacology*; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D026901:Membrane Transport Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger / Q000096:biosynthesis*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins; D014365:Tryptophan Hydroxylase / Q000096:biosynthesis
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D005277:Fenfluramine; D014365:Tryptophan Hydroxylase