Chronic fluoxetine or desmethylimipramine treatment alters 5-HT2 receptor mediated c-fos gene expression

These studies examined the effects of a 21-day treatment regime with either the tricyclic antidepressant, desmethylimipramine (DMI), or the selective 5-HT uptake inhibitor, fluoxetine, on 5-HT₂ receptors in rat brain, as assessed by selective agonist-mediated c-fos gene expression. Chronic, but not acute, treatment with fluoxetine (10 mg/kg, i.p. for 21 days) resulted in supersensitization of the response to an acute challenge (4 mg/kg, i.p.) with the selective 5-HT₂ agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI), both in frontal cortex and in hippocampus. Chronic treatment with DMI (10 mg/kg, i.p. for 21 days) resulted in a significant desensitization of the response to DOI. These findings are discussed in relation to the possible modes of action of these two clinically useful agents.