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 underlying 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‐methyl‐serotonin induced the expression of these early genes in structures including the caudate putamen and nucleus accumbens.