Permanent sexual and regional noradrenergic and dopaminergic systems impairment after prenatal and postnatal exposure to chlordimeform

Abstract

Introduction: Formamidines pesticides have been described to induce permanent effects on development of monoaminergic neurotransmitter systems. The mechanisms that induce these effects are not known but it has been suggested that these effects could be related to monoamino oxidase (MAO) inhibition. Chlordimeform is a formamidine pesticide, which is a very weak inhibitor of MAO although it has been described to induce permanent and sex dependent alterations of serotoninergic system. Objectives and methods: In order to confirm that formamidines induce permanent alterations of monoaminergic neurotransmitter systems regardless of MAO inhibition, the effects of maternal exposure to chlordimeform (5 mg/kg bw, orally) on brain region dopamine and noradrenaline levels of male and female offspring rats at 60 days of age were evaluated. The results showed that chlordimeform induced a significant decrease of noradrenaline and dopamine levels in the prefrontal cortex and striatum and of dopamine levels in the hippocampus, showing an interaction by sex for these regions. Results: Chlordimeform also caused a decrease of DOPAC levels in the striatum and of MHPG and HVA metabolites levels in the prefrontal cortex and striatum. Moreover, it induced an increase in the content of metabolites DOPAC and HVA in the hippocampus and an increase in the metabolite content of DOPAC in the striatum. Lastly, it increased the turnover of DA in the hippocampus and striatum and decreased the turnover of NA and DA in frontal cortex, as well as the NA in striatum. Conclusions: The present findings indicate that maternal exposure to chlordimeform altered dopaminergic and noradrenergic neurochemistry in their offspring in a region and sex dependent way, and those variations confirm that other mechanisms different from MAO inhibition are implicated.