Nowak G, Ordway G A, Paul I A
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Brain Res. 1995 Mar 27;675(1-2):157-64. doi: 10.1016/0006-8993(95)00057-w.
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.
慢性抗抑郁药治疗会导致啮齿动物皮层中NMDA受体复合物的适应性改变。这种适应性改变包括甘氨酸从士的宁不敏感甘氨酸受体上置换[3H]5,7-二氯犬尿氨酸的能力降低，以及高亲和力、可被甘氨酸置换的[3H]CGP-39653与谷氨酸受体结合减少。我们推测，自杀受害者的额叶皮层可能会出现NMDA受体功能障碍。我们现在报告，与年龄和死后间隔相匹配的自杀受害者相比，高亲和力、可被甘氨酸置换的[3H]CGP-39653与谷氨酸受体结合的比例从对照组的45±5%降至27±6%。相比之下，与对照组相比，自杀受害者额叶皮层中甘氨酸抑制[3H]CGP-39653结合的能力和最大效力均未改变。此外，与对照组相比，自杀受害者中甘氨酸抑制[3H]5,7-二氯犬尿氨酸与士的宁不敏感甘氨酸受体结合的能力以及[3H]5,7-二氯犬尿氨酸结合的特异性结合均无差异。同样，与对照组相比，自杀受害者额叶皮层中基础的、甘氨酸或谷氨酸增强的[3H]地佐环平非平衡结合均未改变。这些数据首次证明了支持谷氨酸能功能障碍参与自杀潜在的精神病理学以及人类重度抑郁症这一假设。
