Glutamate receptors in the postmortem striatum of schizophrenic, suicide, and control brains

J. Thomas Noga, Thomas M. Hyde, Mary M. Herman, Christopher F. Spurney, Llewellyn B. Bigelow, Daniel R. Weinberger, Joel E. Kleinman

Research output: Contribution to journalArticlepeer-review

Abstract

Introduction: Previous postmortem studies of glutamate receptors and uptake sites have shown decreased D-aspartate (D-Asp) (a marker for the high affinity glutamate uptake site) and elevated (+)-5-methyl-10,11-dihydro-5H- dibenzo [a,d]cyclohepten-5,10-imine maleate (MK-801) binding in the putamen in schizophrenia and elevated α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA) receptor binding in the caudate nucleus of schizophrenics who committed suicide. The relative effects of schizophrenia, suicide, and neuroleptic treatment in these findings is unclear. This study further explores binding to glutamate receptors (NMDA, kainic acid, and AMPA) and uptake sites in postmortem striatal structures in schizophrenics relative to three control groups (normal controls, neuroleptic-treated controls, and nonpsychotic suicides). Methods: We compared the binding densities of tritium-labeled ligands 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), kainic acid (KA), MK-801, and D-Asp, which target the α-amino-3-hydroxy-5-methyl- 4-isoxazolepropionate (AMPA), KA, and N-methyl-D-aspartic acid (NMDA) ionotropic receptor sites and the glutamate uptake site, respectively, in postmortem striatal/accumbens tissue from six DSM-III-R schizophrenics, eight normal controls, eight neuroleptic-treated controls, and eight suicide victims using standard receptor autoradiographic methods. Results: Binding of [3H]CNQX (AMPA receptors) was significantly different among the four groups across the subdivisions of the striatum: caudate, putamen, and nucleus accumbens (ANOVA P = .0007, .002, and .004, respectively). The schizophrenia group had higher mean CNQX binding in the caudate nucleus than normal (P=.005) and neuroleptic controls (P=.006) but not suicides (P = .6), who were also higher than normals and neuroleptic-treated controls (P = .05). The binding densities of tritiated MK-801, KA, and D-Asp were not significantly different among the four groups of subjects in any of the striatal regions examined. Conclusions: The data suggest there may be an increased density of AMPA receptor sites in the caudate nucleus in schizophrenia that is not apparently due to neuroleptic treatment. A similar increase was also seen the suicide group. Although these data do not confirm previous reports of an increase in [3H]MK-801 or a decrease in [3H]D-Asp binding in the basal ganglia in schizophrenia, the increased caudate AMPA binding observed here could reflect decreased cortical glutamatergic innervation of the caudate. Its implication for suicide is unclear.

Original languageEnglish (US)
Pages (from-to)168-176
Number of pages9
JournalSynapse
Volume27
Issue number3
DOIs
StatePublished - Nov 1 1997
Externally publishedYes

Keywords

  • AMPA
  • D-aspartate
  • Glutamate
  • Kainic acid
  • NMDA
  • Schizophrenia

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'Glutamate receptors in the postmortem striatum of schizophrenic, suicide, and control brains'. Together they form a unique fingerprint.

Cite this