Phenelzine treatment increases transcription factor AP-2 levels in rat brain.
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-2alpha and AP-2beta levels in rat brain. We have also reported an association between a specific genotype of AP-2beta 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-2alpha, AP-2beta and the DNA binding activity of AP-2 in nuclear extracts prepared from rat whole brain when compared with sham treated animals.


CONCLUSIONS
These data suggest that AP-2 is not involved in the therapeutic 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.
Damberg
Mattias
M
Department of Neuroscience, Section of Pharmacology, Uppsala University, Uppsala, Sweden. mattias.damberg@neuro.uu.se
Berggård
Cecilia
C
Oreland
Lars
L
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009841:Oligonucleotides / Q000378:metabolism; D010624:Phenelzine / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013687:Telencephalon / Q000187:drug effects / Q000378:metabolism; D050656:Transcription Factor AP-2; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D008996:Monoamine Oxidase Inhibitors; D009841:Oligonucleotides; D020033:Protein Isoforms; D050656:Transcription Factor AP-2; D014157:Transcription Factors; D010624:Phenelzine