Differential long-term effects of developmental exposure to polychlorinated biphenyls 52, 138 or 180 on motor activity and neurotransmission. Gender dependence and mechanisms involved.
Developmental exposure to polychlorinated biphenyls (PCBs) induces motor alterations in humans by unknown mechanisms. It remains unclear whether: (a) all non-dioxin-like (NDL) PCBs are neurotoxic or it depends on the grade of chlorination; (b) they have different neurotoxicity mechanisms; (c) they affect differently males and females. The aims of this work were to assess: (1) whether perinatal exposure to 3 NDL-PCBs with different grades of chlorination, (PCBs 52, 138 or 180) affects differentially motor activity in adult rats; (2) whether the effects are different in males or females and (3) the mechanisms involved in impaired motor activity. Rats were exposed to PCBs from gestational day 7 to post-natal day 21. Experiments were performed when the rats were 4 months-old. PCB52 did not affect motor activity, PCB180 reduced it in males but not in females and PCB138 reduced activity both in males and females. PCB52 or 138 did not affect extracellular dopamine in nucleus accumbens (NAcc). PCB180 increased it both in males and females. Extracellular glutamate in NAcc was reduced by the three PCBs. Activation of metabotropic glutamate receptors (mGluRs) in NAcc increased extracellular dopamine in control rats and in those exposed to PCB52 and reduced dopamine in rats exposed to PCB180. In rats exposed to PCB138 activation of mGluRs increases dopamine in females and reduces it in males. The opposite changes were observed for glutamate. mGluRs activation reduced extracellular glutamate in control rats and in those exposed to PCB52 and increased glutamate in rats exposed to PCB180. In rats exposed to PCB138 activation of mGluRs reduces glutamate in females and increases it in males. The data support that different NDL-PCBs affect differently motor activity. Increased glutamate release in NAcc following activation of mGluRs would be involved in reduced dopamine release and reduced motor activity in rats exposed to PCB138 or 180.
Laboratory of Neurobiology, Centro de Investigacion Principe Felipe, Valencia, Spain.
Jordi
J
Boix
Omar
O
Cauli
Heather
H
Leslie
Vicente
V
Felipo
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D012727:Sex Characteristics; D009435:Synaptic Transmission / Q000187:drug effects*
D017470:Receptors, Glutamate; C009407:2,5,2',5'-tetrachlorobiphenyl; D018698:Glutamic Acid; C410127:PCB 180; D008734:Methoxyhydroxyphenylglycol; C029790:2,2',3',4,4',5-hexachlorobiphenyl; D011078:Polychlorinated Biphenyls; C010117:3,4-dihydroxyphenylglycol; D004298:Dopamine