Noradrenergic lesion antagonizes desipramine-induced adaptation of NMDA receptors.
Repeated administration of the tricyclic antidepressant, desipramine, for 28 days to mice effected a decrease in the potency of glycine to displace [3H]5,7-dichlorokynurenic acid (5,7-DCKA) in mouse cortical homogenates. Pre-treatment with the noradrenergic neurotoxin DSP-4, while having no effect alone, attenuated the desipramine-induced effect. The present findings support a norepinephrine-dependent adaptation of the NMDA receptor complex in vivo following chronic desipramine treatment. The inter-relationship of norepinephrine and glutamate transmission may provide insight into the mechanism underlying the action of antidepressant drugs.
Harkin
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A
Laboratory of Neurobehavioral Pharmacology, Division of Neurobiology and Behavior Research, Department of Psychiatry, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, USA.
Nowak
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G
Paul
I A
IA
D000222:Adaptation, Physiological; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001596:Benzylamines / Q000633:toxicity; D002540:Cerebral Cortex / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D005473:Fluoxetine / Q000031:analogs & derivatives / Q000378:metabolism; D005998:Glycine / Q000494:pharmacology; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D051379:Mice; D009638:Norepinephrine / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000502:physiology
D000929:Antidepressive Agents, Tricyclic; D001596:Benzylamines; D016194:Receptors, N-Methyl-D-Aspartate; D005473:Fluoxetine; C011386:nisoxetine; D007736:Kynurenic Acid; C012102:DSP 4; C066192:5,7-dichlorokynurenic acid; D005998:Glycine; D003891:Desipramine; D009638:Norepinephrine