Effects of Chronic Lamotrigine Administration on Maximal Electroshock- Induced Seizures in Mice

The aim of the study was to determine anticonvulsant activity of lamotrigine (LTG) after acute and chronic treatment in four different protocols against maximal electroshock-induced seizures in mice. Such a knowledge seems to be valuable in view of the fact that all interactions between LTG and other drugs are evaluated in acute, not chronic, experiments. Electroconvulsions were produced by means of alternating current (50 Hz, 25 mA, 0.2 s) delivered via ear-clip electrodes. Motor impairment and long-term memory deficits in animals were assessed in the chimney test and in passive avoidance task, respectively. Brain and plasma concentrations of LTG were measured by HPLC. Chronic treatment with LTG (2 injections for 14 days) significantly potentiated the anticonvulsant effects of this antiepileptic in the maximal electroshock test in mice, significantly decreasing ED50 value for this antiepileptic. No impairment in motor coordination or long-term memory after acute or chronic treatment with LTG was noted. Nevertheless, prolonged treatment aggravated toxicity of LTG assessed in the chimney test as TD50 value. Repeated administration of LTG significantly increased plasma and brain concentrations of the antiepileptic drug when compared to the control group (single drug application). In conclusion, anticonvulsant action of LTG in the maximal electroshock test in mice may change, depending on the length of therapy. Both acute and chronic protocols are necessary in preclinical assessment of the anticonvulsant effects of drugs and possible interactions between them.