Endogenous melatonin and epileptogenesis: facts and hypothesis

In human epilepsy, diurnal variation in seizure phenomena suggests the involvement of a time-dependent biological signal. Clinical evidence indicates that in some cases, temporal clustering of epileptic seizures is in phase with the nocturnal rise in circulating melatonin. Although this hormone has been reported to stabilize the brain against seizure-producing stimuli, these pharmacological doses are not representative of physiological conditions but would nonetheless facilitate widespread inhibitory neurotransmission characteristic of traditional anticonvulsants. Instead, it is proposed that endogenous melatonin contributes to epileptiform activity through inhibitory actions on dopaminergic activity. Dopamine is considered a natural downregulator of seizure activity in a number of species, including humans, and numerous lines of evidence suggest that melatonin is capable of stimulating a decrease in dopamine output within areas of the brain thought to participate in the control of epileptic seizures. Pharmacological manipulation of the endogenous melatonin rhythm may provide a useful therapeutic strategy against the occurrence of seizures during increased hormone production.