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.
Tilakaratne
N
N
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129, USA.
Yang
Z
Z
Friedman
E
E
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D005473:Fluoxetine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D016762:Genes, fos / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D012313:RNA / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D000662:Amphetamines; D000929:Antidepressive Agents, Tricyclic; D003891:Desipramine; D005473:Fluoxetine; D007650:Ketanserin; D012313:RNA; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine