Antidepressant-like effect of lamotrigine is reversed by veratrine: a possible role of sodium channels in bipolar depression.
Lamotrigine has been found to be efficacious in the acute management of bipolar depression and long-term management of bipolar disorder, especially in delaying depressive recurrence, either as monotherapy or as adjunctive therapy. Lamotrigine is also an antiepileptic drug, and is efficient in the treatment of focal epilepsies. It is thought to act by inhibition of glutamate release through blockade of voltage-sensitivity sodium channels and stabilization of the neuronal membrane.


OBJECTIVE
The scope of this study was to determinate if sodium channels are important for lamotrigine and other antidepressant to exert their antidepressant-like function.


METHODS
This study assessed the effects of veratrine, a Na(+) channel opener on antidepressant effect of lamotrigine and others antidepressants: two tricyclic antidepressants (TCAs): imipramine, a mixed serotonergic noradrenergic reuptake inhibitor, desipramine, a specific noradrenergic reuptake inhibitor and a SSRI: paroxetine, the most potent selective serotonergic reuptake inhibitor, using an animal model of depression, the forced swimming test. Veratrine (0.125 mg/kg) and lamotrigine (16, 32 mg/kg) or antidepressants (16, 32 mg/kg) were given i.p. 45 and 30 min, respectively, before the test.


RESULTS
We observed that when combined with veratrine the antidepressant-like effect of lamotrigine was reversed, but the antidepressant-like effect of the imipramine, desipramine and paroxetine was not changed, indicating that the mechanism of action of lamotrigine is different from that of antidepressants.
Prica
Corina
C
EA 3256 Neurobiologie de l'anxiété et de la dépression, Faculté de Médecine, 1 rue Gaston Veil, BP 53508, 44035 Nantes Cedex 01, France.
Hascoet
Martine
M
Bourin
Michel
M
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001714:Bipolar Disorder / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D046353:Immobility Response, Tonic / Q000187:drug effects; D000077213:Lamotrigine; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming; D014227:Triazines / Q000627:therapeutic use*; D014702:Veratrine / Q000494:pharmacology*
D000928:Antidepressive Agents; D014227:Triazines; D014702:Veratrine; D000077213:Lamotrigine