Topiramate and phenytoin anti-immobility effect in the mice forced swimming test is reversed by veratrine: Implication for bipolar depression treatment.
Topiramate and phenytoin possess mood stabilizing properties. The mechanism of action of anticonvulsants used in the treatment of bipolar depression is complex and still not completely elucidated. Na(+) channels are present at distinct sites in neurons, where they sub serve different functions and play distinct roles. The fact that most of the anticonvulsants used in the treatment of bipolar disorders are blockers of voltage-gated Na channels has determined our interest in evaluating the role of ion channels in bipolar disorders.


OBJECTIVE
The scope of this study was to determinate if sodium channels are important for topiramate and phenytoin to exert their antidepressant-like functioning.


METHODS
The role of Na(+) channels in the mechanism of action of the anticonvulsants was investigated by using veratrine a selective activator of Na channels in a mice model of depression, the forced swimming test. Veratrine 0.125 mg/kg and topiramate or phenytoin (16 and 32 mg/kg) were given IP 45 and 30 min, respectively, before the test.


RESULTS
The administration of topiramate and phenytoin induce a decrease in the immobility time on the FST which can be considered as an antidepressant-like activity. The antidepressant-like effect of the anticonvulsants was completely reversed by veratrine suggesting that the antidepressant-like effect of topiramate and phenytoin on the FST might be due to their Na(+) channels blocking properties.
Bourin
Michel
M
EA 3256 Neurobiologie de l'anxiété et de la dépression, Faculté de Médecine, BP 53508, 1 Rue Gaston Veil, F44035 Nantes Cedex 01, France. michel.bourin@univ-nantes.fr
Chenu
Franck
F
Hascoët
Martine
M
D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001714:Bipolar Disorder; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D008124:Locomotion / Q000187:drug effects; D008297:Male; D049990:Membrane Transport Modulators / Q000494:pharmacology*; D051379:Mice; D009483:Neuropsychological Tests; D010672:Phenytoin / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D062687:Sodium Channel Agonists; D015222:Sodium Channels / Q000378:metabolism; D013550:Swimming; D013997:Time Factors; D000077236:Topiramate; D014702:Veratrine / Q000494:pharmacology*
D000928:Antidepressive Agents; D049990:Membrane Transport Modulators; D062687:Sodium Channel Agonists; D015222:Sodium Channels; D000077236:Topiramate; D005632:Fructose; D010672:Phenytoin; D014702:Veratrine