Melatonin, a hormone produced in the pineal gland and released into th
e general circulation on a diurnal basis, has been implicated in many
behavioral processes, where it has been shown to have anxiolytic, seda
tive, and anticonvulsant effects. Male gerbils (Meriones unguiculatus)
injected daily with melatonin (25 mu g, s,c.) exhibited a reduced sei
zure response to pentylenetetrazol (PTZ, 60 mg/kg, s.c.). The present
studies determined 1) whether melatonin's effect was related to the ti
me of day that it was administered and 2) whether a single acute injec
tion of melatonin at various doses could produce anticonvulsant activi
ty. Gerbils provided with 13 weeks of daily melatonin injections (25 m
u g, s.c,) exhibited fewer convulsions after PTZ treatment irrespectiv
e of the time of day melatonin was injected. In addition, the melatoni
n-treated gerbils had lower mortality rates (1/12) than the untreated
or vehicle-injected gerbils (5/12). On the other hand, single acute in
jections of melatonin (0.1-10 mg/kg, i.p,) produced no anticonvulsant
activity. It appears that the anticonvulsant effects of melatonin occu
r only after the animals are chronically exposed to the indole. In add
ition, melatonin's anticonvulsant ability may utilize a different mech
anism than those involved in its endocrine effects, since no diurnal d
ifference in melatonin's anticonvulsant activity was observed.