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

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,...

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Main Authors: Paul J. Fitzgerald, Chris Barkus, Michael Feyder, Lisa M. Wiedholz, Yi-Chyan Chen, Rose-Marie Karlsson, Rodrigo Machado-Vieira, Carolyn Graybeal, Trevor Sharp, Carlos Zarate, Judith Harvey-White, Jing Du, Rolf Sprengel, Peter Gass, David Bannerman, Andrew Holmes
Format: Article
Language:English
Published: Elsevier 2010-12-01
Series:Neurobiology of Disease
Subjects:
Glutamate
Mouse
Stress
Anxiety
Mania
Dopamine
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996110002603
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spelling doaj-c358207d2b2245629e0f61c262b048b42021-03-22T12:35:47ZengElsevierNeurobiology of Disease1095-953X2010-12-01403608621Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder?Paul J. Fitzgerald0Chris Barkus1Michael Feyder2Lisa M. Wiedholz3Yi-Chyan Chen4Rose-Marie Karlsson5Rodrigo Machado-Vieira6Carolyn Graybeal7Trevor Sharp8Carlos Zarate9Judith Harvey-White10Jing Du11Rolf Sprengel12Peter Gass13David Bannerman14Andrew Holmes15Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USA; Corresponding author. Section on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, 5625 Fishers Lane Room 2N09, Bethesda, MD 20852-9411, USA. Fax: +1 301 480 1952.Department of Experimental Psychology, South Parks Road, University of Oxford, UKSection on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USASection on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USADepartment of Psychiatry, Buddhist Tzu Chi General Hospital, Taipei Branch, Taipei, TaiwanSection on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USALaboratory of Molecular Pathology, National Institute of Mental Health, Bethesda, MD, USASection on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USADepartment of Pharmacology, Mansfield Road, University of Oxford, UKMood and Anxiety Disorders Research Program, National Institute of Mental Health, Bethesda, MD, USANeuroendocrinology Section, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USALaboratory of Molecular Pathology, National Institute of Mental Health, Bethesda, MD, USAMax Planck Institute for Medical Research, Heidelberg, GermanyDepartment of Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, GermanyDepartment of Experimental Psychology, South Parks Road, University of Oxford, UKSection on Behavioral Science and Genetics, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, USAGlutamatergic 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.http://www.sciencedirect.com/science/article/pii/S0969996110002603GlutamateMouseStressAnxietyManiaDopamine
collection DOAJ
language English
format Article
sources DOAJ
author Paul J. Fitzgerald
Chris Barkus
Michael Feyder
Lisa M. Wiedholz
Yi-Chyan Chen
Rose-Marie Karlsson
Rodrigo Machado-Vieira
Carolyn Graybeal
Trevor Sharp
Carlos Zarate
Judith Harvey-White
Jing Du
Rolf Sprengel
Peter Gass
David Bannerman
Andrew Holmes
spellingShingle Paul J. Fitzgerald
Chris Barkus
Michael Feyder
Lisa M. Wiedholz
Yi-Chyan Chen
Rose-Marie Karlsson
Rodrigo Machado-Vieira
Carolyn Graybeal
Trevor Sharp
Carlos Zarate
Judith Harvey-White
Jing Du
Rolf Sprengel
Peter Gass
David Bannerman
Andrew Holmes
Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder?
Neurobiology of Disease
Glutamate
Mouse
Stress
Anxiety
Mania
Dopamine
author_facet Paul J. Fitzgerald
Chris Barkus
Michael Feyder
Lisa M. Wiedholz
Yi-Chyan Chen
Rose-Marie Karlsson
Rodrigo Machado-Vieira
Carolyn Graybeal
Trevor Sharp
Carlos Zarate
Judith Harvey-White
Jing Du
Rolf Sprengel
Peter Gass
David Bannerman
Andrew Holmes
author_sort Paul J. Fitzgerald
title 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_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_sort does gene deletion of ampa glua1 phenocopy features of schizoaffective disorder?
publisher Elsevier
series Neurobiology of Disease
issn 1095-953X
publishDate 2010-12-01
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.
topic Glutamate
Mouse
Stress
Anxiety
Mania
Dopamine
url http://www.sciencedirect.com/science/article/pii/S0969996110002603
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