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.