Lack of effects of chlordecone on synthesis rates, steady state levels and metabolites of catecholamines in rat brain.

Reports on effects of chlordecone on brain catecholamine concentrations have been inconsistent. Because various studies indicate the potential for toxic effects on neurotransmitter systems, the following study was performed to assess effects of chlordecone on brain adrenergic systems. Male Sprague-Dawley rats dosed once with chlordecone at 100 mg/kg were sacrificed after 24 hr, then brain norepinephrine (NE) and dopamine (DA) levels were assayed. Another group was fed chlordecone at 10 mg/kg for 10 days. Additionally, animals treated with 10 mg/kg/day were injected iv with 3H-tyrosine at two intervals prior to sacrifice in order to estimate NE and DA synthesis rates. Whole brain concentrations of NE, DA, 3,4-dihydroxyphenylacetic acid (DOPAC) and 3-methoxy-4-hydroxyphenylglycol sulfate (MOPEG-SO4) were measured. No changes were observed in whole brain catecholamine or metabolite concentrations, nor in NE or DA synthesis rates. In another experiment, administration of chlordecone (10 mg/kg for 10 days) was found not to alter the rate of incorporation of 3H-tyrosine into NE or DA in any brain area tested. Results suggest that the initial functional deficits responsible for neurological symptoms do not result from inhibition of synthesis and transport of brain catecholamines.