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Interaction Between the Serotoninergic and Dopaminergic Systems in d ‐Fenfluramine‐Induced Activation of c‐ fos and junB Genes in Rat Striatal Neurons
Author(s) -
Gardier A. M.,
Moratalla R.,
Cuéllar B.,
Sacerdote M.,
Guibert B.,
Lebrec H.,
Graybiel A. M.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0741363.x
Subject(s) - dopaminergic , striatum , serotonergic , endocrinology , medicine , fenfluramine , c fos , sch 23390 , dynorphin , immediate early gene , agonist , chemistry , dopamine , biology , neuroscience , serotonin , receptor , gene expression , opioid peptide , biochemistry , opioid , gene
To test for the relative contributions of the dopaminergicand serotoninergic systems in the striatum to the effects of d ‐fenfluramine, an indirect serotonin receptor agonist, we assessedthe expression of Fos/Jun proteins induced by d ‐fenfluramine givenalone or in the presence of dopaminergic or serotoninergic agents. Todetermine the neuronal targets of d ‐fenfluramine in the striatum, weidentified the phenotypes of striatal neurons in which d ‐fenfluramineinduced Fos expression. Our results demonstrated that d ‐fenfluramineevokes nuclear expression of Fos/Jun B proteins in the striatum, and that theFos expression was dose‐dependent and accompanied by transient induction ofc‐ fos mRNA. Fos expression was blocked by p ‐chloroamphetamine, a serotoninergic neurotoxin. Pretreatment withSCH 23390, a D 1 ‐dopamine receptor antagonist, led to a markeddecrease in Fos/Jun B expression in the caudoputamen, but not in the cortex,whereas pretreatment with methiothepin, a nonselective serotonin5‐HT 1 receptor antagonist, blocked Fos expression completely in thecortex and only partially in the caudoputamen. The expression of Fos/Jun B inthe striatum occurred mainly in dynorphin‐containing neurons and in asubpopulation of striatal interneurons that exhibited NADPH‐diaphoraseactivity. Most of the enkephalin‐containing neurons of the striatum did notshow Fos/Jun B staining. These results suggest that the mechanism by which d ‐fenfluramine induces c‐ fos and jun B expression in the rat caudoputamen depends at least in part on activation of the dopaminergic system by serotonin.