Basic Science

Abstract

Abstract The hormone melatonin has been reported to exhibit antiepileptic properties in clinical trials. However, recent animal studies have demonstrated that melatonin can have opposite effects on brain function, depending on the dose and timing of melatonin administration. In other words, although high pharmacologic doses are able to decrease brain excitability and suppress seizures, smaller doses of melatonin (administered at night when melatonin levels in the brain are highest), similar in amount to what is produced by the brain, can actually increase the excitability of neurons, making them more susceptible to seizure activity. In this study, we used an animal model of epilepsy to study the effects of melatonin on seizure development. We made two important observations: (a) seizures induced by the drug pilocarpine occurred with a shorter latency at night (when brain melatonin levels are highest) than during the day, and (b) when small doses of drug that block melatonin receptors are injected directly into the hippocampus, an area of the brain important for the development and spread of seizures, then seizures during the night were delayed. Furthermore, this effect was reversed by a drug that blocks the activity of GABA, the major inhibitory neurotransmitter in the brain, suggesting that melatonin may decrease GABA-receptor function in the hippocampus. Although we did not study the effects of melatonin directly, our data suggest that endogenous melatonin may enhance brain excitability and contribute to the development of epileptic seizures. This process may be involved with certain forms of nocturnal epilepsy and may raise a caution for persons with epilepsy who take melatonin. Epilepsia 2005;46(4).