Demontis, Francesca and Falconi, Marcella and Canu, Desirèe and Serra, Gino (2015) Memantine prevents "bipolar-like" behavior induced by chronic treatment with imipramine in rats. European Journal of Pharmacology, Vol. 752 , p. 49-54. ISSN 0014-2999. Article.
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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.
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