Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder?
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,...
| Những tác giả chính: | , , , , , , , , , , , , , , , |
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| Định dạng: | Journal article |
| Ngôn ngữ: | English |
| Được phát hành: |
2010
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| _version_ | 1826296815662661632 |
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| author | Fitzgerald, P Barkus, C Feyder, M Wiedholz, L Chen, Y Karlsson, R Machado-Vieira, R Graybeal, C Sharp, T Zarate, C Harvey-White, J Du, J Sprengel, R Gass, P Bannerman, D Holmes, A |
| author_facet | Fitzgerald, P Barkus, C Feyder, M Wiedholz, L Chen, Y Karlsson, R Machado-Vieira, R Graybeal, C Sharp, T Zarate, C Harvey-White, J Du, J Sprengel, R Gass, P Bannerman, D Holmes, A |
| author_sort | Fitzgerald, P |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T04:22:09Z |
| format | Journal article |
| id | oxford-uuid:cb61ecd6-01dd-48dd-9e6f-c9cc5bf5e67f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:22:09Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:cb61ecd6-01dd-48dd-9e6f-c9cc5bf5e67f2022-03-27T07:14:28ZDoes gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder?Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cb61ecd6-01dd-48dd-9e6f-c9cc5bf5e67fEnglishSymplectic Elements at Oxford2010Fitzgerald, PBarkus, CFeyder, MWiedholz, LChen, YKarlsson, RMachado-Vieira, RGraybeal, CSharp, TZarate, CHarvey-White, JDu, JSprengel, RGass, PBannerman, DHolmes, AGlutamatergic 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. |
| spellingShingle | Fitzgerald, P Barkus, C Feyder, M Wiedholz, L Chen, Y Karlsson, R Machado-Vieira, R Graybeal, C Sharp, T Zarate, C Harvey-White, J Du, J Sprengel, R Gass, P Bannerman, D Holmes, A Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder? |
| title | Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder? |
| title_full | Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder? |
| title_fullStr | Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder? |
| title_full_unstemmed | Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder? |
| title_short | Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder? |
| title_sort | does gene deletion of ampa glua1 phenocopy features of schizoaffective disorder |
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