Neonatal exposure to paraquat or MPTP induces permanent changes in striatum dopamine and behavior in adult mice.
We have recently reported that environmental toxicants, such as DDT, PCBs, pyrethroids, and nicotine can induce permanent functional and neurochemical changes in adult mice when given to neonatal mice during the peak of rapid brain growth. In the present investigation the neurotoxic effects following neonatal exposure to paraquat (N,N'-dimethyl-4,4'-bipyridylium), a broad-spectrum herbicide with structural similarity to the 1-methyl-4-phenylpyridium ion (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which can induce Parkinson's syndrome, and MPTP were studied. Five groups of mice were given paraquat or MPTP orally: group 1, vehicle; groups 2 and 3, MPTP 0.3 and 20 mg/kg; groups 4 and 5, paraquat 0.07 and 0.36 mg/kg when 10 and 11 days old. Neonatal spontaneous motor activity was tested on Day 18 in mice given paraquat 0.36 mg/kg body wt. Adult spontaneous motor activity testing was performed at ages 60 and 120 days. On Day 125 the mice were decapitated and the contents of dopamine (DA), serotonin (5-HT), and metabolites in striatum were analyzed. The results may be summarized as follows: (1) No signs of acute toxicity or differences in weight gain were observed in any of the groups. Nor was any respiratory distress or motor performance dysfunction evident on Day 18 in mice given paraquat 0.36 mg/kg body wt. (2) The behavioral tests at 60 days of age showed a marked hypoactive condition in the mice given paraquat (at both doses) and MPTP (at both doses). (3) At the age of 120 days the hypoactive behavior persisted and appeared even more pronounced. (4) The high doses of MPTP and paraquat--and to a less extent the low doses--reduced the striatal content of DA and metabolites without affecting 5-HT. The altered behavior, together with the dose-dependent reduction of DA and metabolites in neostriata in this study, further demonstrates the susceptibility to low-dose exposure to environmental pollutants during the neonatal period.
Fredriksson
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Department of Toxicology, Uppsala University, Sweden.
Fredriksson
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Eriksson
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D000818:Animals; D000831:Animals, Newborn; D003342:Corpus Striatum / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D020267:MPTP Poisoning; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D010269:Paraquat / Q000633:toxicity*; D012701:Serotonin / Q000378:metabolism
D012701:Serotonin; D010269:Paraquat; D004298:Dopamine