Lithium-methomyl induced seizures in rats: A new model of status epilepticus?

Journal Article · Thu Mar 15 04:00:00 EDT 2007 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2006.09.017· OSTI ID:20976876

Kaminski, Rafal M ^[1]; Blaszczak, Piotr ^[1]; Dekundy, Andrzej ^[1]; Parada-Turska, Jolanta ^[2]; Calderazzo, Lineu ^[3]; Cavalheiro, Esper A ^[3]; Turski, Waldemar A ^[1]

---

1. Department of Toxicology, Institute of Agricultural Medicine, Jaczewskiego 2, 20-950 Lublin (Poland)
2. Department of Rheumatology and Connective Tissue Diseases, Medical University, Jaczewskiego 8, 20-090 Lublin (Poland)
3. Department of Neurology and Neurosurgery, Laboratory of Experimental Neurology, Escola Paulista de Medicina, R. Botucatu 862, BR-04023 Sao Paulo, S.P. (Brazil)

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.

• OSTI ID: 20976876
• Journal Information: Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2-3 Vol. 219; ISSN TXAPA9; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CARBAMATES
INSECTICIDES
LETHAL DOSES
LITHIUM
LITHIUM CHLORIDES
PILOCARPINE
RATS
TRITIUM