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.
Nowak
G
G
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Li
Y
Y
Paul
I A
IA
D000222:Adaptation, Physiological; D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D016194:Receptors, N-Methyl-D-Aspartate; D015283:Citalopram; D005998:Glycine