Proconvulsant action of diethyldithiocarbamate in stimulation of the perforant path.
The ability of diethyldithiocarbamate (DEDTC) to prolong electrical afterdischarge (AD) and lower the threshold for behavioral seizures elicited by stimulation of the perforant path (PPS) was examined. DEDTC was given in doses of 25, 50, and 100 mg/kg, IP. The effects of DEDTC on the threshold for wet dog shakes (WDS) and the number of WDS elicited by PPS were inconsistent. It had no effect on the duration of AD accompanied with WDS. However, DEDTC, at both 50 and 100 mg/kg, significantly lowered the threshold for rearing accompanied with forelimb clonus. At 100 mg/kg, it also prolonged the duration of AD occurring with these seizures. The effects of DEDTC were transitory and coincided with the time course for its ability to chelate the mossy fiber intravesicular pool of zinc (i.e., that which is released by activation of dentate granule cells). It is suggested that release of zinc from the mossy fibers may serve to protect the hippocampus from paroxysmal seizure activity.
Laboratory of Molecular and Integrative Neuroscience, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709.
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Mitchell
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Barnes
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002614:Chelating Agents / Q000494:pharmacology; D003292:Convulsants / Q000633:toxicity*; D004050:Ditiocarb / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects; D006651:Histocytochemistry; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D015032:Zinc / Q000097:blood / Q000502:physiology
D002614:Chelating Agents; D003292:Convulsants; D004050:Ditiocarb; D015032:Zinc