Caenorhabditis elegans is a useful model for examining metabolic processes and related mechanisms. We here examined the effect of exposure to N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone (6-PPDQ) on dopamine metabolism and underling molecular basis in nematodes. The dopamine content was reduced by 6-PPDQ (1 and 10&#
xa0;&#
x3bc;g/L). Meanwhile, dopamine related behaviors (basal slowing response and area restricted searching) were changed by 6-PPDQ (1 and 10&#
xa0;&#
x3bc;g/L). Exposure to 6-PPDQ (1 and 10&#
xa0;&#
x3bc;g/L) decreased expressions of genes (
cat-2 and
bas-1) encoding enzymes governing dopamine synthesis and
cat-1 encoding dopamine transporter. Development of dopaminergic neurons was also affected by 10&#
xa0;&#
x3bc;g/L 6-PPDQ as reflected by decrease in fluorescence intensity, neuronal loss, and defect in dendrite development. Exposure to 6-PPDQ (1 and 10&#
xa0;&#
x3bc;g/L) altered expressions of
ast-1 and
rcat-1 encoding upregulators of
cat-2 and
bas-1. The dopamine content and expressions of
cat-2 and
bas-1 were inhibited by RNAi of
ast-1 and increased by RNAi of
rcat-1 in 6-PPDQ exposed nematodes. Using endpoints of locomotion behavior and brood size, in 6-PPDQ exposed nematodes, the susceptibility to toxicity was caused by RNAi of
ast-1,
cat-2,
bas-1, and
cat-1, and the resistance to toxicity was induced by RNAi of
rcat-1. Therefore, 6-PPDQ exposure disrupted dopamine metabolism and the altered molecular basis for dopamine metabolism was associated with 6-PPDQ toxicity induction. Moreover, the defects in dopamine related behaviors and toxicity on locomotion and reproduction could be rescued by treatment with 0.1&#
xa0;mM dopamine.