Chronic lamotrigine treatment increases rat hippocampal GABA shunt activity and elevates cerebral taurine levels

The mechanism of action of the antiepileptic drug lamotrigine has previousl y been investigated only in acute experiments and is thought to involve inh ibition of voltage-dependent sodium channels. However, lamotrigine is effec tive against more forms of epilepsies than other antiepileptic drugs that a lso inhibit sodium channels. We investigated whether chronic lamotrigine tr eatment may affect cerebral amino acid levels. Rats received lamotrigine, 1 0 mg/kg/day, for 90 days. The hippocampal level of GABA increased 25%, and the activities of glutamate decarboxylase and succinic semialdehyde/GABA tr ansaminase increased 12 and 21% (p < 0.05). respectively, indicating increa sed GABA turnover. The uptake of GABA and glutamate into proteoliposomes re mained unaltered. The level of taurine increased 27% in the hippocampus and 16% in the frontal and parietal cortices. The activities of hexokinase and <alpha>-ketoglutarate dehydrogenase, remained at control values. Serum lam otrigine was 41.7 +/- 1.5 muM (mean +/- S.E.M.), which is within the range seen in epileptic patients. Acute experiments with 5, 20 or 100 mg lamotrig ine/kg, caused no changes in brain amino acid levels. The results suggest t hat chronic lamotrigine treatment increases GABAergic activity in the hippo campus. The cerebral increase in taurine, which has neuromodulatory propert ies, may contribute to the antiepileptic effect of lamotrigine. (C) 2001 El sevier Science B.V. All rights reserved.