Chronic pharmacological treatment with certain antidepressants alters the expression and DNA-binding activity of transcription factor AP-2

Several of the genes in the serotonergic and the dopaminergic systems have consensus binding sites for the AP-2 transcription factor family in their r egulatory regions. Imbalances in these systems have been implicated in many psychiatric disorders, including depression and bipolar affective disorder . We have made an effort to further elucidate the molecular mechanisms of d rugs used for affective disorders. Recently, we analyzed the effects of chr onic treatment with certain antidepressants on AP-2 in rat brain. The prese nt study demonstrates that chronic administration of three different classe s of antidepressants modulates the DNA-binding activity of AP-2 in the rat brain. Chronic administration of citalopram (10 mg/kg), imipramin (10 mg/kg ) and lithium-chloride (40 mg/kg) significantly decreased DNA-binding activ ity of AP-2. Furthermore, citalopram (10 mg/kg) and imipramin (10 mg/kg) si gnificantly decreased the amount of AP-2 alpha protein as determined by ELI SA. In addition, citalopram (10 mg/kg) significantly decreased the amount o f AP-2 beta protein. In contrast, chronic administration of lithium-chlorid e (40 mg/kg) did not affect the amount of the two AP-2 isoforms. An increas ed under standing of the function of transcription factors and their involv ement in human disease, such as depression, could make it possible in the f uture to selectively modulate relevant target genes directly. (C) 2000 Else vier Science Inc. All rights reserved.