Adaptation of cortical but not hippocampal NMDA receptors after chronic citalopram treatment.

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.