Dual monoamine modulation for the antidepressant-like effect of lamotrigine in the modified forced swimming test

Lamotrigine is an anticonvulsant drug that exhibits a clinical antidepressant effect. However, few studies have been conducted with lamotrigine in animal models of depression and its mechanism of antidepressant action is still unclear. The present study evaluates the effect of lamotrigine (5–20 mg/kg, i.p.) in the modified forced swimming test and compare its behavior pattern in the test with those of paroxetine (20 mg/kg, i.p.), nortriptyline (20 mg/kg, i.p.) and dizolcipine–MK-801 (0.1 mg/kg, i.p.). The effect of lamotrigine on locomotor activity and memory was also studied in order to exclude false-positive results. At low doses, lamotrigine (10 mg/kg) decreased immobility and increased climbing scores, a similar pattern to nortriptyline. A higher lamotrigine dose (20 mg/kg) also increased swimming scores. Lamotrigine neither changed locomotion in the open-field test nor impaired habituation. Paroxetine and dizolcipine decreased immobility and increased swimming. Dizolcipine also decreased climbing. However, although the effects of paroxetine and nortriptyline were seen without effect on locomotor activity, dizolcipine increased locomotor activity. The present study indicates that the antidepressant-like effect of lamotrigine is probably related to noradrenergic/serotonergic systems.