Behavioral, electroencephalographic (EEG) and neuropathological effects of
methomyl, a
carbamate insecticide reversibly inhibiting
acetylcholinesterase activity, were studied in naive or
lithium chloride (24 h, 3 mEq/kg, s.c.) pretreated male Wistar rats. In naive animals,
methomyl with equal potency produced motor limbic
seizures and fatal
status epilepticus. Thus, the CD50 values (50%
convulsant dose) for these seizure endpoints were almost equal to the LD50 (50% lethal dose) of
methomyl (13 mg/kg).
Lithium pretreated rats were much more susceptible to
convulsant, but not lethal effect of
methomyl. CD50 values of
methomyl for motor limbic
seizures and
status epilepticus were reduced by
lithium pretreatment to 3.7 mg/kg (a 3.5-fold decrease) and 5.2 mg/kg (a 2.5-fold decrease), respectively. In contrast,
lithium pretreatment resulted in only 1.3-fold decrease of LD50 value of
methomyl (9.9 mg/kg). Moreover,
lithium-
methomyl treated animals developed a long-lasting
status epilepticus, which was not associated with imminent lethality observed in
methomyl-only treated rats.
Scopolamine (10 mg/kg) or
diazepam (10 mg/kg) protected all
lithium-
methomyl treated rats from convulsions and lethality. Cortical and hippocampal EEG recordings revealed typical epileptic discharges that were consistent with behavioral
seizures observed in
lithium-
methomyl treated rats. In addition, convulsions induced by
lithium-
methomyl treatment were associated with widespread neurodegeneration of limbic structures. Our observations indicate that
lithium pretreatment results in separation between
convulsant and lethal effects of
methomyl in rats. As such,
seizures induced by
lithium-
methomyl administration may be an alternative to
lithium-
pilocarpine model of
status epilepticus, which is associated with high lethality.