EFFECT OF CARBAMAZEPINE, OXCARBAZEPINE AND LAMOTRIGINE ON THE INCREASE IN EXTRACELLULAR GLUTAMATE ELICITED BY VERATRIDINE IN RAT CORTEX ANDSTRIATUM

Lamotrigine, carbamazepine and oxcarbazepine inhibit veratrine-induced neurotransmitter release from rat brain slices in concentrations corr esponding to those reached in plasma or brain in experimental animals or humans after anticonvulsant doses, presumably due to their sodium c hannel blocking properties. Microdialysis measurements of extracellula r glutamate and aspartate were carried out in conscious rats in order to investigate whether corresponding effects oc cur in vivo. Veratridi ne (10 mu M) was applied via the perfusion medium to the cortex and th e corpus striatum in the presence of the glutamate uptake inhibitor L- trans-pyrrolidine-2,4-dicarboxylic acid (1 mM in perfusion medium). Ma ximally effective anticonvulsant doses of carbamazepine (30 mg/kg), ox ycarbazepine (60 mg/kg) and lamotrigine (15 mg/kg) were given orally. The uptake inhibitor increased extracellular glutamate and aspartate a bout 2-fold in striatum and about 7-fold and 3-fold, respectively, in cortex. Veratridine caused a further 2-3-fold increase in extracellula r glutamate in striatum and cortex, respectively, but its effect on ex tracellular aspartate was less marked in both areas. None of the antic onvulsant compounds affected the veratridine-induced increases in extr acellular glutamate or aspartate in the striatum which were, however, markedly inhibited by tetrodotoxin (1 mu M) and thus are sensitive to sodium channel blockade. In the cortex, the same drugs at the same dos es did cause about 50% inhibition of the veratridine-induced increase in extracellular glutamate. Carbamazepine and to a lesser extent lamot rigine, but not oxcarbazepine, also inhibited the veratridine-induced increase in extracellular aspartate in the cortex.