Docosahexaenoic acid prevents resistance to antiepileptic drugs in two animal models of drug-resistant epilepsy

Objectives: One-third of epileptic patients are resistant to antiepileptic drugs. Few clinical studies with small sample size indicate that polyunsaturated fatty acids could control drug-resistant epilepsy. We examined the efficacy of acute and chronic administration of docosahexaenoic acid (DHA) in two animal models of drug-resistant epilepsies, i.e. 6-Hz psychomotor seizures in mice and lamotrigine (LTG)-resistant kindled rats.Methods: Mice received a single injection of DHA (300 µM, i.c.v.) along with phenytoin (PHT) or LTG (i.p.). Six-Hz electroshock (0.2 milliseconds rectangular pulse width, 3 seconds duration, 44 mA current) was given 15 minutes after DHA, and seizure behaviors were recorded. In LTG-resistant kindled rats, a single dose of DHA (300 µM, i.c.v.) was administered with LTG, and seizure parameters were measured. In chronic treatment, mice received DHA (0.1 g/day, orally) for 30 days. Then, a single dose of LTG or PHT was administered to mice and 6-Hz-induced seizures were recorded. In ra...