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Journal Article

Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder?


Sprengel,  Rolf
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

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Fitzgerald, P. J., Barkus, C., Feyder, M., Wiedholz, L. M., Chen, Y.-C., Karlsson, R.-M., et al. (2010). Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder? Neurobiology of Disease, 40(3), 608-621. doi:10.1016/j.nbd.2010.08.005.

Cite as: http://hdl.handle.net/11858/00-001M-0000-002C-56B2-7
Glutamatergic dysfunction is strongly implicated in schizophrenia and mood disorders. GluA1 knockout (KO) mice display schizophrenia- and depression-related abnormalities. Here, we asked whether GluA1 KO show mania-related abnormalities. KO were tested for behavior in approach/avoid conflict tests, responses to repeated forced swim exposure, and locomotor responses under stress and after psychostimulant treatment. The effects of rapid dopamine depletion and treatment with lithium or a GSK-3β inhibitor (SB216763) on KO locomotor hyperactivity were tested. Results showed that KO exhibited novelty- and stress-induced locomotor hyperactivity, reduced forced swim immobility and alterations in approach/avoid conflict tests. Psychostimulant treatment and dopamine depletion exacerbated KO locomotor hyperactivity. Lithium, but not SB216763, treatment normalized KO anxiety-related behavior and partially reversed hyperlocomotor behavior, and also reversed elevated prefrontal cortex levels of phospho-MARCKS and phospho-neuromodulin. Collectively, these findings demonstrate mania-related abnormalities in GluA1 KO and, combined with previous findings, suggest this mutant may provide a novel model of features of schizoaffective disorder.