Effect of inferior olive lesion on seizure threshold in the rat

Cerebellar stimulation has been associated with anticonvulsant activity in several experimental seizure models. We examined the effect of destruction of cerebellar climbing fibers, by systemic administration of 3-acetylpyridine (3AP) or electrothermic lesion of the inferior olive, on seizures produced by various chemical convulsants in rats. We found that inferior olive lesioned rats had lower threshold to seizures induced by strychnine and brucine, both glycine antagonists. The dose response curve for strychnine seizure was shifted 2.5 times to the left in 3AP lesioned rats. No difference in seizure threshold was seen when picrotoxin, bicuculline or pentylenetetrazole PTZ) were used to produce seizures. Abnormal motor behavior (AMB) including myoclonus, backward movement and hyperextension, produced by all of the convulsants tested, was significantly aggravated in 3AP pretreated rats. The inferior olive-climbing fiber projection to the cerebellum appears to modulate seizures induced by inhibition of glycinergic neurotransmission.