Evaluation of transgenic mice conditionally lacking CREB in noradrenergic neurons as a novel tool for studying its role in the antidepressant drug action

• Autorzy: Rafa-Zablocka K. , Kreiner G. , Baginska M. , Nalepa I.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Most of the current antidepressants modulate levels of monoamines just after administration, however, only after prolonged therapy the clinical effect may be observed. Myriad attempts tried to identify molecular factors responsible for such a delayed response, the prominent example being the cyclic AMP response element binding protein (CREB). Many research suggest that chronically given antidepressants enhance CREB levels and activity. On the other hand, CREB knock-out mice showed rather antidepressant-like behavior, however, the compensatory effects of cAMP response element modulator (CREM) in absence of CREB were not taken into account. In our study we evaluated transgenic mice with selective ablation of CREB in noradrenergic cells, maintained in CREM deficient background (CrebDBHCreCrem-/-) for elucidation of the role of CREB in antidepressant treatment. METHODS: mRNA levels of neurotrophins and α1-adrenoceptors in CrebDBHCreCrem-/- mice were investigated in hippocampus and prefrontal cortex using qPCR method. Next mice were screened in behavioral tests like: open field (OF), tail suspension test (TST) and rotarod. Preliminary TST after acute desipramine (DMI) administration (20 mg/kg, ip) was executed. RESULTS: CrebDBHCreCrem-/- mutant mice did not show any abnormalities in their basal phenotype, moreover the mRNA levels of studied genes were not changed either. However, preliminary experiments revealed that CrebDBHCreCrem-/- show a treatment-resistant phenotype after acute DMI administration in TST, (effect absent in single mutants). CONCLUSIONS: Our results provide further evidence for the important role of CREM as a compensatory factor and indicate that these mice may represent an unique tool to dissect the role of CREB in the mechanism of antidepressants. Supported by statutory funds of the Institute of Pharmacology and 2014/13/B/NZ7/02293 grant. K. Rafa-Zabłocka is a holder of scholarship from the KNOW sponsored by MSHE, Poland.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S63-S64

Twórcy

autor

Rafa-Zablocka K.

• Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland

autor

Kreiner G.

• Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland

autor

Baginska M.

• Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland

autor

Nalepa I.

• Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland