Recent evidence suggests that insulin not only induces indirect effect
s due to hypoglycemia but produces direct effects in the central nervo
us system as well. The present study was undertaken to evaluate a poss
ible direct anti seizure activity of insulin against two drug-induced
in vivo seizure models. The hypoglycemic dose response relationship of
insulin revealed that 0.1 U/kg insulin was ineffective to produce any
change on blood glucose levels. This dose of insulin was found to sig
nificantly improve the seizure parameters tested. 3 g/kg glucose was s
imultaneously administered with 1.0 U/kg insulin into mice to countera
ct the hypoglycemic effect of insulin and thus to maintain a normoglyc
emic state. This combination was also shown to improve the seizure par
ameters tested better than 0.1 U/kg and 1.0 U/kg insulin alone. The ou
tcome of 0.1 U/kg insulin and 3 g/kg glucose combination is representa
tive of an additive anti seizure effect due to the combined effects of
exogenous and endogenous insulin. Contrarily, insulin was found to be
ineffective (1.0 U/kg+ 3 g/kg glucose) against strychnine seizures. T
he results were discussed regarding the possible central role of insul
in in seizure modulation.