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 tr...

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Bibliographic Details
Published in:Behavioural brain research 2008-08, Vol.191 (1), p.49-54
Main Authors: Prica, Corina, Hascoet, Martine, Bourin, Michel
Format: Article
Language:English
Subjects:
Adult and adolescent clinical studies
Analysis of Variance
Animals
Antidepressive Agents - therapeutic use
Behavior, Animal - drug effects
Behavioral psychophysiology
Biological and medical sciences
Bipolar depression
Bipolar Disorder - drug therapy
Bipolar disorders
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Interactions
Fundamental and applied biological sciences. Psychology
Immobility Response, Tonic - drug effects
Lamotrigine
Male
Medical sciences
Mood disorders
Motor Activity - drug effects
Neuropharmacology
Pharmacology. Drug treatments
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer
Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease)
Psychology. Psychoanalysis. Psychiatry
Psychology. Psychophysiology
Psychopathology. Psychiatry
Psychopharmacology
Rats
Rats, Wistar
Sodium channels
Swimming
Triazines - therapeutic use
Veratrine
Veratrine - pharmacology
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Summary: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. Objectives: 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.
ISSN:0166-4328
1872-7549
DOI:10.1016/j.bbr.2008.03.007