The serotonergic system modulates the cocaine-induced expression of the immediate early genes egr-1 and c-fos in rat brain.
Transcription regulatory factors are rapidly induced in brain by a wide variety of stimuli and may be important in coordinating changes in gene expression under-lying neuronal plasticity. Using in situ hybridization, we found that acute cocaine administration (20 mg/kg, intraperitoneally (i.p.)) produced a robust induction of both c-fos and egr-1 immediate early genes. Egr-1 messenger RNA induction was highest in the caudate putamen and in the shell of the nucleus accumbens. No significant induction was noticed after injection of fluoxetine, a selective inhibitor of serotonin uptake. Cocaine-induced egr-1 and c-fos expression was substantially reduced in the brain areas from rats in which the serotonergic projections were lesioned by injection of the neurotoxin 5,7-dihydroxytryptamine and in rats that have been injected with tropisetron, an antagonist of the 5-hydroxytryptamine (5-HT3) receptor. Conversely, the 5-HT3 receptor agonist 2-methylserotonin induced the expression of these early genes in structures including the caudate putamen and nucleus accumbens.
INSERM U338, Strasbourg, France.
N
N
Humblot
N
N
Thiriet
S
S
Gobaille
D
D
Aunis
J
J
Zwiller
D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D003042:Cocaine / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000235:genetics*; D051766:Early Growth Response Protein 1; D015870:Gene Expression / Q000187:drug effects; D005786:Gene Expression Regulation / Q000502:physiology*; D016762:Genes, fos / Q000235:genetics*; D017874:Immediate-Early Proteins; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D017874:Immediate-Early Proteins; D017366:Serotonin Receptor Agonists; D014157:Transcription Factors; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; C045918:2-methyl-5-HT; D003042:Cocaine