title: Memantine prevents "bipolar-like" behavior induced by chronic treatment with imipramine in rats.
abstract: A great deal of evidence suggests that virtually all antidepressant treatments induce a dopaminergic behavioral supersensitivity. We have suggested that this effect may play a key role not only in the antidepressant effect of these treatments, but also in their ability to induce a switch from depression to mania. In 2003-4 we found that the sensitization of dopamine receptors induced by imipramine is followed, after imipramine withdrawal, by a desensitization of these receptors associated with a depressive-like behavior assessed in the forced swimming test. The dopamine receptor sensitization can be prevented by MK-801, an NMDA receptor antagonist, but not by currently used mood stabilizers (lithium, carbamazepine, valproate). These observations led us to suggest - and later confirm - with preliminary clinical observations that memantine may have an acute antimanic and a long-lasting mood-stabilizing effect in treatment-resistant bipolar disorder patients. Here we present data showing that memantine prevents not only the dopamine receptor sensitization induced by imipramine, as observed with MK-801, but also the ensuing desensitization and the associated depressive-like behaviorq observed after antidepressant withdrawal.
authors: Dipartimento di Scienze Biomediche, Università di Sassari, Italy.
authors: Francesca
authors: F
authors: Demontis
authors: Dipartimento di Scienze Biomediche, Università di Sassari, Italy.
authors: Marcella
authors: M
authors: Falconi
authors: Dipartimento di Scienze Biomediche, Università di Sassari, Italy.
authors: Desirèe
authors: D
authors: Canu
authors: Dipartimento di Scienze Biomediche, Università di Sassari, Italy. Electronic address: dsfserra@uniss.it.
authors: Gino
authors: G
authors: Serra
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D007099:Imipramine / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000378:metabolism; D013550:Swimming; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D011954:Receptors, Dopamine; D007099:Imipramine; D008559:Memantine
keywords: Antimanic; Bipolar disorder; Dopamine receptors; Memantine; Mood stabilizer