Chronic citalopram treatment induces time-dependent changes in the expression and DNA-binding activity of transcription factor AP-2 in rat brain.
Imbalances in the midbrain monoaminergic systems have been implicated to play a role in neuropsychiatric conditions. Several genes in these systems have binding sites for transcription factor activating protein-2 (AP-2) in their regulatory regions. Thus, AP-2 may be a factor controlling the expression of genes in the monoaminergic systems important for maintaining normal psychiatric functions. The present study indicates that subchronic treatment with the antidepressant citalopram induces time-dependent changes in DNA-binding activity and levels of transcription factor AP-2 in rat whole brain. Rats were treated with citalopram (10 mg/kg) for 1, 3, 7 and 21 days. Animals treated for 7 days had significantly decreased DNA-binding activity and levels of AP-2 alpha and AP-2 beta isoforms when compared to saline-treated animals. There was no observed difference between citalopram- and saline-treated animals after 21 days. Elucidation of the molecular mechanisms underlying mental disorders is important for future drug development, where transcription factors might be important drug targets.
Berggård
C
C
Department of Neuroscience, Unit of Pharmacology, Uppsala University, PO Box 593 BMC, SE-751 24, Uppsala, Sweden.
Damberg
M
M
Oreland
L
L
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay / Q000379:methods; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D015870:Gene Expression / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics
D000928:Antidepressive Agents; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D015283:Citalopram