The anticonvulsant properties of melatonin on kindled seizures in rats

The literature suggesting that the pineal gland and the indolamine, melatonin, have a significant role in regulating and modulating brain electrical activity is reviewed. The anticonvulsant properties of melatonin were investigated by testing acute doses of melatonin against two types of kindled Scizures in the rat. Against the electrically kindled amygdaloid Scizure, melatonin significantly reduced afterdischarge length at a non-sedative dose, but failed to modify Scizure rank scores. With larger doses of melatonin, which were associated with some sedation and ataxia, the Scizure rank score was reduced, but there was no additional reduction of afterdischarge length. Naloxone treatment (20 mg/kg, i.p.) did not reverse the sedation, ataxia, nor the anticonvulsant effects seen with the large dose of melatonin (200 mg/kg, i.p.). Additional animals were kindled with pentylenetetrazol injections (30 mg/kg, i.p.) given at 2-3 day intervals. Melatonin significantly reduced Scizure rank scores in these kindled animals at one dose (150 mg/kg, i.p.). A larger dose, associated with sedation and ataxia, did not result in any further reduction of Scizure rank scores. For comparison, large and small doses of both phenobarbital and diazepam were also tested against the pentylenetetrazol kindled Scizures. Neither phenobarbital (30 mg/kg) nor diazepam (2.5 mg/kg) induced a neurological deficit; however, both agents reduced Scizure rank to approximately the same score as did melatonin (150 mg/kg). This is the first report of a substantial anticonvulsant property of parenteral melatonin in two animal models of epilepsy. It would appear tha melatonin is most effective against the kindled pentylenetetrazol Scizure, and somewhat less effective against the electrically kindled amygdaloid Scizure. Further testing in other Scizure models and species is needed to define better the anticonvulsant profile of melatonin.