Adaptation of the NMDA receptor in rat cortex following chronic electroconvulsive shock or imipramine.
Chronic (14 days) administration of either imipramine or electroconvulsive shock effected significant changes in the ligand binding properties of the NMDA (N-methyl-D-aspartate) receptor complex in rat cortex. These changes were manifested as: (1) a reduction in the potency of glycine to inhibit the binding of 5,7-dichloro[3H]kynurenic acid to strychnine-insensitive glycine receptors; and (2) a reduction in the proportion of high affinity, glycine-displaceable [3H]CGP-39653 binding to NMDA receptors. Chronic electroconvulsive shock, but not imipramine treatment also reduced the density of [3H]CGP-39653 binding sites in cortical membranes. These findings demonstrate that the ability of chronic antidepressant treatments to induce adaptive changes in the glycine and glutamate regulatory sites of the NMDA receptor is not species specific, since it obtains in rats as well as mice.
Paul
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Laboratory of Neuroscience, NIH/NIDDK, Bethesda, MD 20892-0008.
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Skolnick
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Nowak
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D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004597:Electroshock; D005998:Glycine / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; C069052:CGP 39653; D015763:2-Amino-5-phosphonovalerate; D007736:Kynurenic Acid; D007099:Imipramine; C066192:5,7-dichlorokynurenic acid; D005998:Glycine