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Published on: December 22, 2008
Chronic valproate normalizes behavior in mice overexpressing calcineurin
Claire J Herzog1, Stéphanie Miot, Isabelle M Mansuy
1INSERM U-513, 8 rue de Général Sarrail, 94000, Créteil, France.
European Journal of Pharmacology
|November 21, 2007
Summary
Transgenic expression of calcineurin (PP2B) in mice increases locomotor activity and responses to cocaine, altering anxious behavior. Valproate treatment normalized these calcineurin-induced behavioral changes.
Area of Science:
- Neuroscience
- Molecular Biology
- Psychopharmacology
Background:
- Calcineurin (PP2B) is a crucial Ca(2+)-dependent protein phosphatase in the brain.
- It regulates intracellular signaling pathways involved in synaptic plasticity and complex brain functions.
Purpose of the Study:
- To investigate the role of calcineurin in behavioral responses to novelty and psychostimulants.
- To explore the effects of calcineurin overexpression on anxious-like behavior and its modulation by mood stabilizers.
Main Methods:
- Utilized transgenic mice with overexpressed calcineurin.
- Assessed locomotor activity, behavioral responses to cocaine, and anxious-like behavior.
- Investigated the effects of chronic valproate treatment.
Main Results:
- Transgenic calcineurin expression increased locomotor activity in response to novelty.
- Enhanced behavioral and molecular responses to cocaine were observed.
- Anxious-like behaviors were altered but normalized by chronic valproate treatment.
Conclusions:
- Calcineurin-dependent dephosphorylation significantly influences behavioral reactivity.
- Calcineurin plays a role in the mechanisms of action of mood regulators like valproate.
- Mice overexpressing calcineurin offer a valuable model for studying affective disorders.
