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Updated: Feb 20, 2026
The Tail Suspension Test
Published on: January 28, 2012
Transgenic mice lacking CREB and CREM in noradrenergic and serotonergic neurons respond differently to common
Katarzyna Rafa-Zabłocka1, Grzegorz Kreiner2, Monika Bagińska1
1Department Brain Biochemistry, Institute of Pharmacology, Polish Academy of Sciences, 31-343, Krakow, Smetna 12, Poland.
Abstract:
Evidence exists that chronic antidepressant therapy enhances CREB levels and activity. Nevertheless, the data are not conclusive, as previous analysis of transgenic mouse models has suggested that CREB inactivation in fact contributes to antidepressant-like behavior. The aim of this study was to evaluate the role of CREB in this context by exploiting novel transgenic mouse models, characterized by selective ablation of CREB restricted to noradrenergic (Creb1DBHCre/Crem-/-) or serotonergic (Creb1TPH2CreERT2/Crem-/-) neurons in a CREM-deficient background to avoid possible compensatory effects of CREM. Selective and functional ablation of CREB affected antidepressant-like behavior in a tail suspension test (TST) after antidepressant treatment. Contrary to single Creb1DBHCre mutants, Creb1DBHCre/Crem-/- mice did not respond to acute desipramine administration (20 mg/kg) on the TST. On the other hand, single Creb1TPH2CreERT2 mutants displayed reduced responses to fluoxetine (10 mg/kg) on the TST, while the effects in Creb1TPH2CreERT2/Crem-/- mice differed by gender. Our results provide further evidence for the important role of CREM as a compensatory factor. Additionally, the results indicate that new models based on the functional ablation of CREB in select neuronal populations may represent a valuable tool for investigating the role of CREB in the mechanism of antidepressant therapy.
Insights
This study investigated the role of CREB in antidepressant action using novel mouse models. Selective CREB ablation in specific neurons revealed its crucial involvement in antidepressant-like behaviors, highlighting CREM
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Chronic antidepressant therapy is linked to enhanced CREB (cAMP response element-binding protein) levels and activity.
- Previous studies on transgenic mouse models yielded conflicting results regarding CREB's role in antidepressant-like behavior.
- The involvement of CREB in antidepressant mechanisms requires further elucidation.
Purpose of the Study:
- To investigate the specific role of CREB in antidepressant action.
- To utilize novel transgenic mouse models with selective CREB ablation in noradrenergic and serotonergic neurons.
- To examine CREB's function in antidepressant-like behaviors, considering potential compensatory effects of CREM (cAMP-responsive element modulator).
Main Methods:
- Development of novel transgenic mouse models: Creb1DBHCre/Crem-/- (noradrenergic neuron-specific CREB ablation) and Creb1TPH2CreERT2/Crem-/- (serotonergic neuron-specific CREB ablation) on a CREM-deficient background.
- Assessment of antidepressant-like behavior using the tail suspension test (TST) following administration of desipramine and fluoxetine.
- Analysis of selective and functional CREB ablation effects on behavioral responses to antidepressants.
Main Results:
- Selective and functional ablation of CREB impacted antidepressant-like behavior in the TST.
- Creb1DBHCre/Crem-/- mice showed no response to acute desipramine, unlike single Creb1DBHCre mutants.
- Creb1TPH2CreERT2 mutants exhibited reduced responses to fluoxetine, with gender-specific differences observed in Creb1TPH2CreERT2/Crem-/- mice.
- CREM was identified as a significant compensatory factor.
Conclusions:
- The findings provide evidence for the critical role of CREB in mediating antidepressant-like effects.
- The study underscores the importance of CREM as a compensatory factor in this context.
- The developed transgenic models offer a valuable tool for future research into CREB's role in antidepressant mechanisms.
