Noradrenergic lesion antagonizes desipramine-induced adaptation of NMDA receptors

Repeated administration of the tricyclic antidepressant, desipramine, for 2 8 days to mice effected a decrease in the potency of glycine to displace [H -3]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 supp ort a norepinephrine-dependent adaptation of the NMDA receptor complex in v ivo following chronic desipramine treatment. The inter-relationship of nore pinephrine and glutamate transmission may provide insight into the mechanis m underlying the action of antidepressant drugs. (C) 2000 Elsevier Science B.V. All rights reserved.