Behavioral and neurochemical effects after combined perinatal treatment of rats with lead and disulfiram.

Abstract

Lead exposure during pregnancy and lactation is known to result in various neurochemical and behavioral disturbances. Dithiocarbamates are known to markedly increase lead levels in the brain. However, the neurotoxicity due to combined treatment with lead and dithiocarbamates is not known. Behavioral and neurochemical effects of lead and disulfiram (tetraethylthiuram disulfide) given singly or in combination, were studied in rats. Pregnant rats were treated with lead (0.25% Pb in the drinking water), with disulfiram (0.1 mmol/kg PO twice a week) or with both lead and disulfiram from day 1 of pregnancy until parturition. After parturition the offspring were exposed to lead via the milk of the dams while the disulfiram (0.1 mmol/kg SC twice a week) was given directly to the offspring. At weaning, 26 days after parturition, the treatment was discontinued and after 2 more weeks behavioral and neurochemical studies were started. Neither lead alone nor disulfiram alone caused any significant effects in the behavior activity measurements. However, in combination the two compounds caused an increase in home cage activity and an increased behavioral reactivity as measured in a holeboard apparatus. Extracellular levels of some neurotransmitters and amino acids were measured in the caudate nucleus using the intracerebral dialysis technique. The levels of dopamine were significantly increased in both the lead-treated and the lead plus disulfiram-treated groups. The levels of the metabolites of dopamine (DOPAC and HVA) and serotonin (5-HIAA) were increased in the group treated with lead plus disulfiram.(ABSTRACT TRUNCATED AT 250 WORDS)