Effect of polychlorinated biphenyls on the uptake of dopamine into rat brain synaptic vesicles: A structure-activity study

PCBs are neurotoxic compounds that have a known effect on the dopaminergic system in the brain. In a previous work it was established that PCBs are po tent inhibitors of the uptake of dopamine into rat brain synaptic vesicles. In this work we further investigated the vesicular dopamine uptake in resp onse to different PCBs to explore the structure-activity relationship invol ved in this effect. Twenty PCB congeners were selected, based on multivaria te chemical characterization, to cover the chemical variation within tetra- to hepta-chlorinated PCBs. PCBs of large structural variation were tested and the general finding was that only the ortho-substituted PCBs inhibited the dopamine uptake. The most active congeners were the penta- and hexa-chl orinated PCBs. Furthermore. the uptake was correlated with parameters descr ibing the absolute hardness, the octanol-water partition coefficient, and t he Henry's law constant. These parameters are correlated to the number of c hlorine atoms in ortho positions and to the size of the molecule. Notably t he most active PCBs are highly prevalent in the environment and are dispose d to bioaccumulate in wildlife. Thus, these neurotoxic effects should be in cluded in the risk assessment of PCBS. (C) 2001 Academic Press.