DIETHYLDITHIOCARBAMATE AND BRAIN COPPER

To test the hypothesis that the increase of copper concentration in br ain after diethyldithiocarbamate (DEDTC) administration was due to the formation of a DEDTC-copper complex, able to cross the blood-brain ba rrier, we compared in rats the effects on brain copper of DEDTC given alone, in combination with copper or as a copper-DEDTC complex. The da ily administration for three weeks of DEDTC gone, of DEDTC with copper and DEDTC-copper complex gave the same increase of the level of coppe r in brain. The time course effects of a single administration of DEDT C and of me DEDTC-copper complex were approximately the same : after a delay of about 24 h, there was an increase in brain copper concentrat ions which persisted for at least three days.This delayed effect expla ins discrepancies found in the literature concerning changes of copper in brain after a single administration of DEDTC according to the time interval between administration and tissue sampling. The results show that the additional copper does not increase the effect of DEDTC and that the formation of a DEDTC-copper lipophilic complex which could cr oss the blood-brain barrier is probably not the mechanism responsible for the increase of brain copper induced by DEDTC. Mechanisms other th an direct copper chelation may be involved.