title: Swimming impairment and acetylcholinesterase inhibition in zebrafish exposed to copper or chlorpyrifos separately, or as mixtures.
abstract: Pesticides such as chlorpyrifos (CPF) and metals such as copper can impair swimming behavior in fish. However, the impact to swimming behavior from exposure to mixtures of neurotoxicants has received little attention. In the current study, we analyzed spontaneous swimming rates of adult zebrafish (Danio rerio) to investigate in vivo mixture interactions involving two chemical classes. Zebrafish were exposed to the neurotoxicants copper chloride (CuCl, 0.1 μM, 0.25 μM, 0.6 μM, or 6.3, 16, 40 ppb), chlorpyrifos (CPF, 0.1 μM, 0.25 μM, 0.6 μM, or 35, 88, 220 ppb) and binary mixtures for 24h to better understand the effects of Cu on CPF neurotoxicity. Exposure to CPF increased the number of animals undergoing freeze responses (an anti-predator behavior) and, at the highest CPF dose (0.6 μM), elicited a decrease in zebrafish swimming rates. Interestingly, the addition of Cu caused a reduction in the number of zebrafish in the CPF exposure groups undergoing freeze responses. There was no evidence of additive or synergistic toxicity between Cu and CPF. Although muscle AChE activity was significantly reduced by CPF, there was a relatively poor relationship among muscle AChE concentrations and swimming behavior, suggesting non-muscle AChE mechanisms in the loss of swimming behavior. In summary, we have observed a modulating effect of Cu on CPF swimming impairment that appears to involve both AChE and non-AChE mechanisms. Our study supports the utility of zebrafish in understanding chemical mixture interactions and neurobehavioral injury.
authors.affiliation: Department of Environmental and Occupational Health Sciences, School of Public Health, University of Washington, Seattle, Washington 98105-6099, USA.
authors.forename: Fred A
authors.initials: FA
authors.lastname: Tilton
authors.forename: Theo K
authors.initials: TK
authors.lastname: Bammler
authors.forename: Evan P
authors.initials: EP
authors.lastname: Gallagher
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004390:Chlorpyrifos / Q000633:toxicity*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D003300:Copper / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009420:Nervous System / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects; D013550:Swimming; D014874:Water Pollutants, Chemical / Q000633:toxicity; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D002800:Cholinesterase Inhibitors; D014874:Water Pollutants, Chemical; D003300:Copper; D000110:Acetylcholinesterase; D004390:Chlorpyrifos