Nowak G, Li Y, Paul I A
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Eur J Pharmacol. 1996 Jan 4;295(1):75-85. doi: 10.1016/0014-2999(95)00585-4.
Chronic treatment with citalopram produced a 6.2-fold reduction in the proportion of high affinity glycine-displaceable [3H]CGP-39653 binding sites and a 1.5-fold reduction in the potency of glycine to inhibit [3H]5,7-dichlorokynurenic acid binding in mouse cortex but not in hippocampus. Chronic citalopram also increased the aspartate concentration by 110% in cortex and 33% in hippocampus, and increased the glycine/threonine concentration by 33% in hippocampus. These results support the hypotheses that: (1) the adaptation of strychnine-insensitive glycine recognition sites and the allosteric coupling of the glycine and glutamate recognition sites are independently regulated by chronic antidepressant treatment; (2) chronic antidepressant administration induces regionally selective adaptation of the NMDA receptor complex; and (3) antidepressant-induced adaptation of the NMDA receptor complex may be mediated by regionally selective changes in excitatory amino acid concentration.
西酞普兰长期治疗使小鼠皮质中高亲和力甘氨酸置换型[3H]CGP - 39653结合位点的比例降低了6.2倍，使甘氨酸抑制[3H]5,7 - 二氯犬尿氨酸结合的效力降低了1.5倍，但在海马体中未出现这种情况。长期使用西酞普兰还使皮质中的天冬氨酸浓度增加了110%，海马体中的增加了33%，并使海马体中的甘氨酸/苏氨酸浓度增加了33%。这些结果支持以下假设：(1) 士的宁不敏感的甘氨酸识别位点的适应性以及甘氨酸和谷氨酸识别位点的变构偶联受慢性抗抑郁治疗的独立调节；(2) 慢性抗抑郁药给药诱导NMDA受体复合物的区域选择性适应性变化；(3) 抗抑郁药诱导的NMDA受体复合物适应性变化可能由兴奋性氨基酸浓度的区域选择性变化介导。
