Expression of NMDAR1, GluR1, GluR7, and KA1 Glutamate Receptor mRNAs Is Decreased in Frontal Cortex of “Neuroleptic‐Free” Schizophrenics: Evidence on Reversible Up‐Regulation by Typical Neuroleptics

• Published in: Journal of neurochemistry Vol. 71; no. 6; pp. 2454 - 2464
• Main Author: Sokolov, Boris P.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.12.1998; Blackwell
• Subjects: Adult and adolescent clinical studies; Aged; Aged, 80 and over; Aging - metabolism; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - therapeutic use; Biological and medical sciences; Brain - metabolism; Female; Frontal cortex; Frontal Lobe - metabolism; Glutamate receptor mRNAs; Humans; Hydrogen-Ion Concentration; Male; Medical sciences; Middle Aged; Neuroleptic; Postmortem; Postmortem Changes; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; Receptors, Glutamate - genetics; Receptors, N-Methyl-D-Aspartate - genetics; Reference Values; RNA, Messenger - metabolism; Schizophrenia; Schizophrenia - drug therapy; Schizophrenia - metabolism; Sex Characteristics; Psychosis; Human; Neuroleptic; Central nervous system; Postmortem; Schizophrenia; Glutamate receptor; Frontal cortex; Gene expression; NMDA receptor; Brain (vertebrata); Kainate receptor
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.1998.71062454.x

: Schizophrenics exhibit abnormalities in many memory‐associated functions mediated by the frontal cortex. Glutamate receptors play key roles in learning and memory. Hence, abnormalities in glutamate receptors within the frontal cortex may be associated with schizophrenia. In addition, emerging evidence indicates that glutamate receptors may be involved in the actions of antipsychotic drugs. To test these hypotheses, we measured mRNAs encoding the NMDAR1, GluR1, GluR7, and KA1 subunits of glutamate receptor in the left superior frontal gyrus from 21 elderly schizophrenics with varying histories of antipsychotic drug treatment and nine normal drug‐free elderly controls. There were significant negative correlations between NMDAR1, GluR1, GluR7, and KA1 mRNA levels and time without neuroleptic medication before death in schizophrenics, indicating that levels of the glutamate receptor mRNAs decline rapidly after drug withdrawal. Further analysis revealed that in “neuroleptic‐free” (>6 months) schizophrenics, levels of NMDAR1, GluR1, GluR7, and KA1 mRNAs were significantly lower than in controls. By contrast, in schizophrenics who were receiving neuroleptics until death, levels of NMDAR1, GluR1, GluR7, and KA1 mRNAs did not differ significantly from controls. These findings indicate that decreased levels of NMDAR1, GluR1, GluR7, and KA1 mRNAs may be present in the frontal cortex of some schizophrenics and that typical neuroleptics may reversibly increase levels of these mRNAs.