Interaction between the serotoninergic and dopaminergic systems in d-fenfluramine-induced activation of c-fos and jun B genes in rat striatal neurons

被引:25
作者
Gardier, AM
Moratalla, R
Cuéllar, B
Sacerdote, M
Guibert, B
Lebrec, H
Graybiel, AM
机构
[1] CSIC, Inst Cajal Neurobiol, Madrid 28002, Spain
[2] Univ Paris Sud, Fac Pharm, IFR ISIT, Lab Neuropharmacol UPRES EAD MENRT, Chatenay Malabry, France
[3] Univ Paris Sud, Fac Pharm, IFR ISIT, Lab Toxicol,INSERM,U461, Chatenay Malabry, France
[4] Univ Picardie, Fac Pharm, Pharmacol Lab, Amiens, France
[5] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA
关键词
dexfenfluramine; striatum; c-fos; jun B; dynorphin; p-chloroamphetamine;
D O I
10.1046/j.1471-4159.2000.0741363.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To test for the relative contributions of the dopaminergic and serotoninergic systems in the striatum to the effects of d-fenfluramine, an indirect serotonin receptor agonist, we assessed the expression of Fos/Jun proteins induced by d-fenfluramine given alone or in the presence of dopaminergic or serotoninergic agents. To determine the neuronal targets of d-fenfluramine in the striatum, we identified the phenotypes of striatal neurons in which d-fenfluramine induced Fos expression. Our results demonstrated that d-fenfluramine evokes nuclear expression of Fos/Jun B proteins in the striatum, and that the Fos expression was dose-dependent and accompanied by transient induction of c-fos mRNA. Fos expression was blocked by p-chloroamphetamine, a serotoninergic neurotoxin. Pretreatment with SCH 23390, a D-1-dopamine receptor antagonist, led to a marked decrease in Fos/Jun B expression in the caudoputamen, but not in the cortex, whereas pretreatment with methiothepin, a nonselective serotonin 5-HT1 receptor antagonist, blocked Fos expression completely in the cortex and only partially in the caudoputamen, The expression of Fos/Jun B in the striatum occurred mainly in dynorphin-containing neurons and in a subpopulation of striatal interneurons that exhibited NADPH-diaphorase activity. Most of the enkephalin-containing neurons of the striatum did not show 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.
引用
收藏
页码:1363 / 1373
页数:11
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