Research Article| Volume 30, ISSUE 12, P1191-1198, December 15, 1991

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Deficient NMDA-mediated glutamate release from synaptosomes of schizophrenics

  • A.D. Sherman
    Address reprint request to A.D. Sherman, Department of Psychiatry, The University of Iowa, College of Medicine, 500 Newton Road, Iowa City, IA 52242.
    Department of Psychiatry, The University of Iowa, College of Medicine, Iowa City, USA
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  • T.S. Hegwood
    Department of Psychiatry, The University of Iowa, College of Medicine, Iowa City, USA
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  • S. Baruah
    Department of Psychiatry, The University of Iowa, College of Medicine, Iowa City, USA
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  • R. Waziri
    Department of Psychiatry, The University of Iowa, College of Medicine, Iowa City, USA
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  • Author Footnotes
    ∗∗ We thank Dr. Robert Robinson and Dr. Nancy Andreasen for their support. We also thank Dr. Wallace Tourtellote and his staff, who sent us the brain samples from the National Neurological Brain Band, VAMC, Wadsworth Division, Los Angeles, California 90073, which is sponsored by NINDS/NIMH, National Multiple Sclerosis Society, Huntington's Disease Foundation, Comprehensive Epilepsy Program, Tourette Syndrome Association, Dystonia Medical Research Foundation, Veterans Health Services and Research Administration, Department of Veteran Affairs.
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      Previous studies from our laboratory indicated that the veratridine-induced release of glutamate and GABA from synaptosomes derived from brains of schizophrenics was decreased. In the present study, synaptosomes were prepared from frozen brain samples from schizophrenics and from controls. Stimulation by 10 μmol/L 2-amino-3-hydroxy-5-methoxylisoxazole-4-propionic acid (AMPA) produced equal glutamate release from both groups. Release induced by either 10 μmol/L kainic acid (KA) or n-methyl-d-asparate (NMDA) was reduced significantly in the preparations derived from schizophrenics. Similarly, the amount of GABA released by 50 μmol/L glutamate was also reduced in the schizophrenic-derived synaptosomes. However, in membranes derived from the crude synaptosomal pellet, no differences between the controls and schizophrenics were observed in measures of total glutamate binding or its displacement by NMDA. The data demonstrate a deficiency in NMDA (and possibly KA) receptor functioning in schizophrenics and support the “second-generation” theories of schizophrenia as a glutamatergic deficiency disorder.
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