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Chronic valproate normalizes behavior in mice overexpressing calcineurin


Herzog, C J; Miot, S; Mansuy, I M; Giros, B; Tzavara, E T (2008). Chronic valproate normalizes behavior in mice overexpressing calcineurin. European Journal of Pharmacology, 580(1-2):153-160.

Abstract

Calcineurin (PP2B) is a Ca2+-dependent protein phosphatase enriched in the brain that takes part in intracellular signaling pathways regulating synaptic plasticity and complex brain functions. We report here that when these pathways are activated by transgenic expression of calcineurin, locomotor activity of mice in response to novelty is increased, as well as the behavioral and molecular responses of the psychostimulant cocaine. We also observed that the anxious-like behavior is altered. These behavioral changes are indicative of a generally increased behavioral responsiveness and could be normalized by chronic treatment with the mood stabilizer valproate. These results provide proof of concept that calcineurin-dependent dephosphorylation plays an important role in behavioral reactivity and in the effects of mood regulators. Mice overexpressing calcineurin represent a novel tool to study affective responses related to psychiatric disorders.

Abstract

Calcineurin (PP2B) is a Ca2+-dependent protein phosphatase enriched in the brain that takes part in intracellular signaling pathways regulating synaptic plasticity and complex brain functions. We report here that when these pathways are activated by transgenic expression of calcineurin, locomotor activity of mice in response to novelty is increased, as well as the behavioral and molecular responses of the psychostimulant cocaine. We also observed that the anxious-like behavior is altered. These behavioral changes are indicative of a generally increased behavioral responsiveness and could be normalized by chronic treatment with the mood stabilizer valproate. These results provide proof of concept that calcineurin-dependent dephosphorylation plays an important role in behavioral reactivity and in the effects of mood regulators. Mice overexpressing calcineurin represent a novel tool to study affective responses related to psychiatric disorders.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Brain Research Institute
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:February 2008
Deposited On:29 Dec 2008 10:31
Last Modified:04 Jan 2018 08:21
Publisher:Elsevier
ISSN:0014-2999
Publisher DOI:https://doi.org/10.1016/j.ejphar.2007.10.050
PubMed ID:18021766

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