Dithiocarb (N,N-diethyldithiocarbamate, DEDTC) decreases levels of biogenic monoamines in the adult mouse brain

What is it about?

Dithiocarb (diethyldithiocarbamate, DEDTC) belongs to the group of dithiocarbamates (DTCs) and is the main metabolite of disulfiram, the drug currently used for treatment of alcohol dependence. Its therapeutic effect on alcohol addiction is mediated by an unpleasant aversive reaction due to increased acetaldehyde levels in blood and tissues after ingestion of alcohol. This effect is accompanied by neurological complications such as neurobehavioral symptoms. Most of these can be attributed to the impairment of the metabolism of brain biogenic amines and therefore to alterations in neurotransmitter pathways. To gain new insights into the dithiocarbamates and their effects on neurotransmitter systems, an in vivo experimental model based on daily injections of DEDTC in adult mice for seven days was established. To this end, the concentration of the three major brain monoamines, dopamine (DA), noradrenaline (NA) and serotonin (5-HT), was measured in the whole brain with High-performance liquid chromatography (HPLC), revealing a decrease in all of them; with the exception of noradrenaline, which maintained its constant levels. Moreover, using immunohistochemical and western blot methods, a decline in enzymes such as tyrosine hydroxylase (TH), dopa beta hydroxilase (DBH), choline acetyltransferase (ChAT), and D2 dopamine receptor (D2R) was revealed. All showed evidence of alterations in different neurotransmitter pathways with DEDTC treatment, which would explain some of the neurobehavioral alterations observed in patients treated with disulfiram. Therefore, this experimental model would allow the study of interactions between different neurotransmitter systems, which are clearly modified in neurodegenerative diseases and psychiatric illness.

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