title: Critical duration of exposure for developmental chlorpyrifos-induced neurobehavioral toxicity.
abstract: Developmental exposure of rats to the pesticide chlorpyrifos (CPF) causes persistent neurobehavioral impairment. In a parallel series of studies with zebrafish, we have also found persisting behavioral dysfunction after developmental CPF exposure. We have developed a battery of measures of zebrafish behavior, which are reliable and sensitive to toxicant-induced damage. This study determined the critical duration of developmental CPF exposure for causing persisting neurobehavioral effects. Tests of sensorimotor response (tap startle response and habituation), stress response (novel tank diving test) and learning (3-chamber tank spatial discrimination) were conducted with adult zebrafish after early developmental CPF exposure. The CPF exposure level was 100 ng/ml with durations of 0-1, 0-2, 0-3, 0-4 and 0-5 days after fertilization. Developmental CPF exposure had persisting behavioral effects in zebrafish tested as adults. In the tactile startle test, CPF exposed fish showed decreased habituation to startle and a trend toward increased overall startle response. In the novel tank exploration test, exposed fish showed decreased escape diving response and increased swimming activity. In the 3-chamber learning test, the 0-5 day CPF exposure group had a significantly lower learning rate. There was evidence for persisting declines in brain dopamine and norepinepherine levels after developmental CPF exposure. In all of the measures the clearest persistent effects were seen in fish exposed for the full duration of five days after fertilization. In a follow-up experiment there were some indications for persisting behavioral effects after exposure during only the later phase of this developmental window. This study demonstrated the selective long-term neurobehavioral alterations caused by exposure to CPF in zebrafish. The zebrafish model can facilitate the determination of the molecular mechanisms underlying long-term neurobehavioral impairment after developmental toxicant exposure.
authors: Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
authors: Damiyon
authors: D
authors: Sledge
authors: Jerry
authors: J
authors: Yen
authors: Terrell
authors: T
authors: Morton
authors: Laura
authors: L
authors: Dishaw
authors: Ann
authors: A
authors: Petro
authors: Susan
authors: S
authors: Donerly
authors: Elwood
authors: E
authors: Linney
authors: Edward D
authors: ED
authors: Levin
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D004390:Chlorpyrifos / Q000633:toxicity*; D004195:Disease Models, Animal; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000378:metabolism; D047108:Embryonic Development / Q000187:drug effects*; D004781:Environmental Exposure / Q000009:adverse effects / Q000032:analysis; D007858:Learning / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000196:embryology* / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D013216:Reflex, Startle / Q000187:drug effects; D013997:Time Factors; D015027:Zebrafish / Q000196:embryology* / Q000378:metabolism
chemical_list: D004390:Chlorpyrifos