Inhibitory and Dose-dependent effect of intracerebroventricular docosahexaenoic acid on clonic seizures induced by pentylenetetrazole in mice

Introduction: Epilepsy is one of the most common neurologic disorders. Pharmacoresistance and adverse effects of current antiepileptic drugs (AEDs) necessitate development of new drugs and strategies for treatment of epilepsy. Omega 3-Polyunsaturated fatty acids (ω3-PUFAs) are safe nutritional supplements that recently considered for treatment of epilepsy. Anticonvulsant effect of docosahexaenoic acid (DHA), the most fatty acid in the brain and neural membrane with important role in modulation of neuronal function, is reported by some researchers. In the present study, the anticonvulsant effect of DHA (before conversion to metabolites) was examined in pentylenetetrazole (PTZ) and maximal electroshock (MES) model of seizures. Methods: Different doses of DHA (0.01, 0.03, 0.075, 0.3, 300 and 1000 μM) were injected into lateral cerebral ventricles (i.c.v.) of adult male NMRI mice. After 15min, clonic seizures were induced by PTZ (60 mg/kg, i.p.) or tonic seizures were induced by maximal electroshock (MES, 50mA, 50Hz, 0.5sec duration). Sodium valproate and phenytoin were injected i.p. as positive control groups for PTZ and MES tests, respectively. Latency to seizure occurrence, number of protected mice and any abnormal behavior in mice were recorded. Results: DHA did not show any protective effect in MES model but increased the latency of seizures and inhibited clonic seizures induced by PTZ with ED50 value of 0.1 μM. Conclusion: Acceptable anticonvulsant activity, good tolerability and low price could suggest DHA as a good candidate for design and development of new anticonvulsant medications.