Lamotrigine differently modulates 7-nitroindazole and L-arginine influence on rat maximal dentate gyrus activation

The effects induced on the maximal dentate gyrus activation (MDA) by administering the anticonvulsant lamotrigine (LTG), the selective inhibitor of neuronal nitric oxide synthase 7-nitroindazole (7-NI) and the precursor of nitric oxide (NO) synthesis L-arginine, alone or in combination, were studied in urethane anaesthetized rats. Either 7-NI or LTG alone administration reduced the number of convulsing animals following angular bundle (AB) stimulation; their combined treatment induced a further increase of the anticonvulsant effect as also demonstrated by the decrease of MDA and afterdischarge (AD) durations in the animals still responding to AB stimulation. On the contrary, the injection of L-arginine induced an aggravation of the experimentally-induced paroxystic phenomena as evidenced by the augmentation of MDA and AD durations. LTG in co-administration with L-arginine was able to reverse the pro-convulsant effect induced by L-arginine alone. The results suggest an efficacious interaction between the nitrergic neurotransmission and LTG-induced effects on dentate seizures.