Phenelzine treatment increases transcription factor AP-2 levels in rat brain

Mattias Damberg , Cecilia Berggård and Lars Oreland

Department of Neuroscience, Section of Pharmacology, Uppsala University, Uppsala, Sweden

author email corresponding author email

BMC Pharmacology 2003, 3:10doi:10.1186/1471-2210-3-10


Published:	28 August 2003

Abstract

Background

The elevations of noradrenaline (NA) and serotonin (5-HT) levels in response to acute serotonin reuptake inhibitor (SSRI) or tricyclic antidepressant (TCA) exposure are not consistent with the time course for the therapeutic action of these antidepressants. Thus, neuronal adaptations are needed for the therapeutic effect to arise. Transcription factor Activating Protein –2 (AP-2) is critical for mammalian neural gene expression. Several genes involved in brainstem CNS transmitter systems, especially the monoamines, have AP-2 binding sites in their regulatory regions. We have previously shown that treatment with citalopram and imipramin resulted in a decrease in AP-2α and AP-2β levels in rat brain. We have also reported an association between a specific genotype of AP-2β to personality traits, binge-eating disorder and platelet monoamine oxidase (MAO) activity.

Results

Subchronic administration (10 days) of phenelzine (PLZ) increased the levels of AP-2α, AP-2β and the DNA binding activity of AP-2 in nuclear extracts prepared from rat whole brain when compared with sham treated animals.

Conclusion

These data suggest that AP-2 is not involved in the theraputic effect of antidepressants. Rather, the effects of antidepressants seen on the levels of AP-2 might be involved in the expression of side-effects during the lag-period.