PMID- 9329152
OWN - NLM
STAT- MEDLINE
DCOM- 19971126
LR  - 20131121
IS  - 0887-4476 (Print)
IS  - 0887-4476 (Linking)
VI  - 27
IP  - 3
DP  - 1997 Nov
TI  - Glutamate receptors in the postmortem striatum of schizophrenic, suicide, and 
      control brains.
PG  - 168-76
AB  - 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 alpha-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 alpha-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.
FAU - Noga, J T
AU  - Noga JT
AD  - Department of Psychiatry and Behavioral Sciences, Emory University School of 
      Medicine, Atlanta, Georgia, USA.
FAU - Hyde, T M
AU  - Hyde TM
FAU - Herman, M M
AU  - Herman MM
FAU - Spurney, C F
AU  - Spurney CF
FAU - Bigelow, L B
AU  - Bigelow LB
FAU - Weinberger, D R
AU  - Weinberger DR
FAU - Kleinman, J E
AU  - Kleinman JE
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Synapse
JT  - Synapse (New York, N.Y.)
JID - 8806914
RN  - 0 (Antipsychotic Agents)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, Glutamate)
RN  - 30KYC7MIAI (Aspartic Acid)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 6OTE87SCCW (6-Cyano-7-nitroquinoxaline-2,3-dione)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology
MH  - Antipsychotic Agents/adverse effects/therapeutic use
MH  - Aspartic Acid/metabolism
MH  - Autoradiography
MH  - Basal Ganglia/metabolism/pathology
MH  - Brain Chemistry/*physiology
MH  - Dizocilpine Maleate/metabolism
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Female
MH  - Humans
MH  - Kainic Acid/metabolism
MH  - Male
MH  - Middle Aged
MH  - Neostriatum/*metabolism/pathology
MH  - Receptors, AMPA/metabolism
MH  - Receptors, Glutamate/*metabolism
MH  - Schizophrenia/drug therapy/*metabolism
MH  - *Suicide
EDAT- 1997/11/05 15:28
MHDA- 2000/06/20 09:00
CRDT- 1997/11/05 15:28
PHST- 1997/11/05 15:28 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1997/11/05 15:28 [entrez]
AID - 10.1002/(SICI)1098-2396(199711)27:3<168::AID-SYN2>3.0.CO;2-B [pii]
AID - 10.1002/(SICI)1098-2396(199711)27:3<168::AID-SYN2>3.0.CO;2-B [doi]
PST - ppublish
SO  - Synapse. 1997 Nov;27(3):168-76. doi: 
      10.1002/(SICI)1098-2396(199711)27:3<168::AID-SYN2>3.0.CO;2-B.