Mice lacking the AMPA GluR1 receptor exhibit striatal hyperdopaminergia and 'schizophrenia-related' behaviors

L. M. Wiedholz, W. A. Owens, R. E. Horton, M. Feyder, R. M. Karlsson, K. Hefner, R. Sprengel, T. Celikel, L. C. Daws, A. Holmes

Research output: Contribution to journalArticlepeer-review

148 Scopus citations


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-α-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.

Original languageEnglish (US)
Pages (from-to)631-640
Number of pages10
JournalMolecular psychiatry
Issue number6
StatePublished - Jun 2008


  • AMPA GluR1
  • Dopamine
  • Dopamine transporter
  • Glutamate
  • Hyperactivity
  • Novelty
  • Prepulse inhibition

ASJC Scopus subject areas

  • Molecular Biology
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Mice lacking the AMPA GluR1 receptor exhibit striatal hyperdopaminergia and 'schizophrenia-related' behaviors'. Together they form a unique fingerprint.

Cite this