Neurochemical and behavioral effects of polychlorinated biphenyls in mice.
The effects of polychlorinated biphenyls (PCBs) were assessed on some behavioral and neurochemical parameters in mice. Acute administration of a dose of 500 mg/kg (po) depressed spontaneous motor activity for a period of 15 min to 3 hr. Subchronic dosing of 30 or 100 mg/kg for 14 days was virtually without effect. PCBs given acutely had no effect on motor coordination nor on pentylenetetrazol-induced convulsions. Exposure of isolated mouse brain synaptosomes to PCBs produced a dose-dependent inhibition of neurotransmitter and precursor uptake (IC50 = 10(-5) to 10(-4) M) as well as stimulation of neurotransmitter release (EC50 = 10(-5) to 10(-4) M). Mitochondrial 45Ca2+ uptake was also enhanced (EC50 = 2.8 x 10(-4) M). Disposition of 14C-PCBs in mitochondria and synaptosomes following an oral dose of 500 mg/kg yielded levels comparable to those in isolated mitochondria and synaptosomes incubated with 14C-PCBs at concentrations that altered central neurotransmitter function in vitro.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism; D011078:Polychlorinated Biphenyls / Q000378:metabolism / Q000633:toxicity*; D013574:Synaptosomes / Q000378:metabolism
D018377:Neurotransmitter Agents; D011078:Polychlorinated Biphenyls; D002118:Calcium