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  Mice lacking the AMPA GluR1 receptor exhibit striatal hypodopaminergia and 'schizophrenia−related' behaviors

Wiedholz, L. M., Owens, W. A., Horton, R. E., Feyder, M., Karlsson, R., Hefner, K., et al. (2008). Mice lacking the AMPA GluR1 receptor exhibit striatal hypodopaminergia and 'schizophrenia−related' behaviors. Molecular Psychiatry, 13(6), 631-640. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/17684498.

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MolPsych_13_2008_631.pdf (Any fulltext), 316KB
 
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MolPsych_13_2008_631Suppl.pdf (Supplementary material), 431KB
 
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Wiedholz, Lisa M., Author
Owens, W. A., Author
Horton, R. E., Author
Feyder, Michael, Author
Karlsson, Rose−Marie, Author
Hefner, K., Author
Sprengel, Rolf1, Author           
Celikel, Tansu2, Author           
Daws, L. C., Author
Holmes, Andrew, Author
Affiliations:
1Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              
2Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              

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Free keywords: glutamate, dopamine, AMPA GluR1, novelty, hyperactivity, prepulse inhibition, dopamine transporter
 Abstract: There is growing evidence implicating dysfunctional glutamatergic neurotransmission and abnormal interactions between the glutamate and dopamine (DA) systems in the pathophysiology of various neuropsychiatric disorders including schizophrenia. The present study evaluated knockout (KO) mice lacking the L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) GluR1 receptor subunit for a range of behaviors considered relevant to certain symptoms of schizophrenia. KO showed locomotor hyperactivity during exposure to open field and in response to a novel object, but normal activity in a familiar home cage. Open field locomotor hyperactivity in KO was effectively normalized to WT levels by treatment with the DA antagonist and neuroleptic haloperidol, while locomotor stimulant effects of the NMDA receptor antagonist MK-801 were absent in KO. Social behaviors during a dyadic conspecific encounter were disorganized in KO. KO showed deficits in prepulse inhibition of the acoustic startle response. In vivo chronoamperometric measurement of extracellular DA clearance in striatum demonstrated retarded clearance in KO. These data demonstrate behavioral abnormalities potentially pertinent to schizophrenia in GluR1 KO, together with evidence of dysregulated DA function. Present findings provide novel insight into the potential role of GluR1, AMPA receptors and glutamate x DA interactions in the pathophysiology of schizophrenia and other neuropsychiatric conditions.

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Language(s): eng - English
 Dates: 2007-04-272006-11-272007-06-062007-08-072008-06-01
 Publication Status: Issued
 Pages: 10
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
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Title: Molecular Psychiatry
Source Genre: Journal
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Publ. Info: Houndmills, Hampshire, UK : Stockton Press
Pages: - Volume / Issue: 13 (6) Sequence Number: - Start / End Page: 631 - 640 Identifier: ISSN: 1359-4184
CoNE: https://pure.mpg.de/cone/journals/resource/954925619131