Chronic valproate normalizes behavior in mice overexpressing calcineurin.
Calcineurin (PP2B) is a Ca(2+)-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.
Herzog
Claire J
CJ
INSERM U-513, 8 rue de Général Sarrail, 94000, Créteil, France.
Miot
Stéphanie
S
Mansuy
Isabelle M
IM
Giros
Bruno
B
Tzavara
Eleni T
ET
D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D003042:Cocaine / Q000494:pharmacology; D004195:Disease Models, Animal; D015870:Gene Expression; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D019964:Mood Disorders / Q000188:drug therapy; D009043:Motor Activity / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology*
D018692:Antimanic Agents; D014635:Valproic Acid; D019703:Calcineurin; D003042:Cocaine