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

Journal article

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.

Authors: Fitzgerald, P; Barkus, C; Feyder, M; Wiedholz, L; Chen, Y

• Publication status: Published
• Journal: Neurobiology of disease
• Volume: 40
• Issue: 3
• Pages: 608-621
• Publication date: 2010-12-01
• DOI: 10.1016/j.nbd.2010.08.005
• EISSN: 1095-953X
• ISSN: 0969-9961
• Language: English
• Keywords: Behavior, Animal; Gene Deletion; Central Nervous System Stimulants; Lithium Compounds; Psychotic Disorders; Receptors, AMPA; Mice, Knockout; Phenotype; Mice, Inbred C57BL; Mice; Antimanic Agents; Animals; Disease Models, Animal