Journal
NEUROBIOLOGY OF DISEASE
Volume 40, Issue 3, Pages 608-621Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2010.08.005
Keywords
Glutamate; Mouse; Stress; Anxiety; Mania; Dopamine; Open field test; Elevated plus-maze
Categories
Funding
- NIH (National Institute on Alcohol Abuse and Alcoholism, NIAAA) [Z01-AA000411]
- Deutsche Forschungsgemeinschaft [GA427/8-1, SP602/2-1]
- Wellcome Trust [074385, 087736]
- BBSRC/GSK
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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-3 beta 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. (C) 2010 Elsevier Inc. All rights reserved.
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