Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/44118
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Type: Journal article
Title: Mice lacking the AMPA CluR1 receptor exhibit striatal hyperdopaminergia and 'schizophrenia-related' behaviors
Author: Wiedholz, L.
Owens, W.
Horton, R.
Feyder, M.
Hefner, K.
Sprengel, R.
Celikel, T.
Daws, L.
Holmes, A.
Citation: Molecular Psychiatry, 2008; 5(6):1-10
Publisher: Nature Publishing Group
Issue Date: 2008
ISSN: 1359-4184
1476-5578
Statement of
Responsibility: 
L M Wiedholz, W A Owens, R E Horton, M Feyder, R-M Karlsson, K Hefner, R Sprenge, T Celike, L C Daws and A Holmes
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--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 DA interactions in the pathophysiology of schizophrenia and other neuropsychiatric conditions.
Keywords: glutamate; dopamine; AMPA GluR1; novelty; hyperactivity; prepulse inhibition; dopamine transporter
Description: Published online 7 August 2007.
Rights: © 2008 Nature Publishing Group
RMID: 0020076223
DOI: 10.1038/sj.mp.4002056
Appears in Collections:Pharmacology publications

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