Ethylenebisdithiocarbamate enhances MPTP-induced striatal dopamine depletion in mice

Diethyldithiocarbamate (DDC) has been shown to enhance 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP)-induced striatal dopamine depletion in mice . Surprisingly, although DDC is a prototypic member of a class of compounds called dithiocarbamates (DTCs) that are widely used in industry and agricu lture, only one study has investigated the interaction of dithiocarbamates other than DDC with MPTP. The purpose of the present study was to investiga te whether two other widely used dithiocarbamates, ethylenebisdithiocarbama te (EBDC) and methyldithiocarbamate (MDC), would also enhance MPTP toxicity . The dithiocarbamates were administered to mice intraperitoneally at vario us doses with or without MPTP. Doses were chosen based on the LD50 values f or each compound. DDC was also tested (using a previously reported dose) fo r comparison. Striata were obtained one week later for dopamine measurement s. Consistent with previous reports, DDC produced statistically significant enhancement in MPTP-induced striatal dopamine depletion. EBDC also produce d significant exacerbation of MPTP-induced dopamine depletion. In contrast to DDC and EBDC, MDC failed to enhance the effects of MPTP, even when admin istered at doses of high lethality. Further studies of the dithiocarbamate class of compounds may help to elucidate the mechanism of DDC and EBDC enha ncement of MPTP toxicity. Given the widespread use of these compounds in th e environment such studies may also provide clues to the process of nigrost riatal cell degeneration in Parkinson's disease. (C) 2000 Intox Press, Inc.