Alterations in the N-methyl-D-aspartate (NMDA) receptor complex in the frontal cortex of suicide victims.
Chronic antidepressant treatment results in adaptation of the NMDA receptor complex in the rodent cortex. This adaptation consists of a reduction in the potency of glycine to displace [3H]5,7-dichlorokynurenic acid from strychnine-insensitive glycine receptors and a reduction in high affinity, glycine-displaceable [3H]CGP-39653 binding to glutamate receptors. We hypothesized that dysfunction of NMDA receptors might occur in frontal cortices from human suicide victims. We now report that the proportion of high affinity, glycine displaceable [3H]CGP-39653 binding to glutamate receptors is reduced from 45 +/- 5% in controls to 27 +/- 6% in age- and post-mortem interval-matched suicide victims. In contrast, neither the potency nor the maximum efficacy of glycine to inhibit [3H]CGP-39653 binding is altered in the frontal cortex of suicide victims compared to controls. Moreover, neither the potency of glycine to inhibit [3H]5,7-dichlorokynurenic acid binding to the strychnine-insensitive glycine receptor nor the specific binding of [3H]5,7-dichlorokynurenic acid binding differed in suicide victims compared to controls. Likewise, neither basal nor glycine- or glutamate enhanced non-equilibrium binding of [3H]dizocilpine was altered in the frontal cortex of suicide victims compared to controls. These data represent the first demonstration supporting the hypothesis that glutamatergic dysfunction is involved in psychopathology underlying suicide and, potentially in human major depression.
Nowak
G
G
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Ordway
G A
GA
Paul
I A
IA
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000378:metabolism; D000328:Adult; D016291:Dizocilpine Maleate / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018009:Receptors, Glycine / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013405:Suicide
D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; C069052:CGP 39653; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D007736:Kynurenic Acid; C066192:5,7-dichlorokynurenic acid