effects of dextromethorphan on zebrafish larval development
TRANSCRIPT
tions of executive control processing including performance on an auditorycontinuous performance task (CPT). The CPT was a computerized taskconsisting of 80 randomly-ordered tones representing two different frequen-cies (“high” and “low”); 20 of the trials were target stimuli to which the childwas instructed to respond by pressing themouse button. Prior to the task, eachchild was given practice to an acquisition criterion of 5 consecutive correctresponses. Preliminary analyses of response accuracy, reaction time (RT), anderrors of commission (false alarms) revealed no significant differences inaccuracy or reaction time, although reaction times were slower in the exposedchildren in each drug group compared to the non-exposed. All exposed groupsshowed elevations in the number of false alarms with a significant increase inthe CBZ group (F(1, 76)=7.35; p=0.008) and a marginally significant increasein the PHT group (F(1, 68)=3.37; p=0.07) when compared to the respectivenon-exposed groups. Additional data from other measures of attention andworking memory will also be presented.
doi:10.1016/j.ntt.2009.04.055
NBTS52
The use of developmental neurotoxicity data in pesticiderisk assessments
Kathleen Raffaelea, Jess Rowlandb, Brenda Mayb, Susan Makrisa,Kelly Schumacherd, Louis ScaranocaOffice of Research and Development, U.S. Environmental Protection Agency,Washington, DC, USAbOffice of Pesticide Programs, U.S. Environmental Protection Agency, Washington,DC, USAcOffice of Pollution Prevention and Toxics, U.S. Environmental Protection Agency,Washington, DC, USAdRegion 7, U.S. Environmental Protection Agency, Kansas City, KS, USA
Following passage of the Food Quality Protection Act, which increasedfocus on potential toxicity of pesticides to children, the number of guidelinedevelopmental neurotoxicity (DNT) studies (OPPTS 870.6300) submitted tothe US Environmental Protection Agency Office of Pesticide Programs (OPP)was greatly increased. To evaluate the impact of available DNT studies onindividual chemical risk assessments, the ways in which data from thesestudies are being used in pesticide risk assessment was investigated. Inaddition, neurobehavioral and neuropathological parameters affected at thelowest observed adverse effect level (LOAEL) for each study were evaluatedto ascertain whether some types of endpoints were consistently moresensitive than others. As of 12/2008, final OPP reviews of DNT studies for 70pesticide chemicals were available: 15 had been used to determine the pointof departure for at least one risk assessment scenario; 15 more weredetermined to have the potential for use as points of departure for future riskassessments. Analysis of parameters affected at study LOAELs found no singleendpoint consistently more sensitive than another. Early assessment timepoints (e.g. PND 11–21) tended to be more sensitive than later time points(PND 60). These results demonstrate that DNT data, when available, canprovide endpoints for risk assessment. Data from these studies affirm theimportance of evaluating a spectrum of behavioral and neuropathologicalendpoints, in young and adult animals, to improve detection of the potentialfor a chemical to cause developmental neurotoxicity. (This abstract does notnecessarily reflect the policy of the USEPA.)
doi:10.1016/j.ntt.2009.04.056
NBTS53
Effects of dextromethorphan on zebrafish larval development
Frank Scalzo, Mike LevineBard College, Annandale-on-Hudson, New York, USA
Dextromethorphan (DXM) is a noncompetitive NMDA receptor antago-nist used in many over-the-counter medications as a cough suppressant.
While it has been shown that DXM has teratogenic effects in chick embryos,evidence suggests that developmental exposure to DXM in other species isnot deleterious. In an attempt to develop experimental parameters forneurobehavioral testing of DXM in the zebrafish model, we conductedstudies to identify concentrations of DXM that could be used in acute andlong-term exposure experiments. Fertilized zebrafish eggs were treated witheither 0, 200 mg/L or 400 mg/L DXM from 4 h post-fertilization to 172 hpost-fertilization. Observations were made for structural and functionaldevelopment. At 200 mg/L, embryos showed signs of malformations thatincluded edema and scoliosis. At 400 mg/L, a significant number of embryosdid not survive; surviving embryos displayed edema and scoliosis. In bothgroups, edema and scoliosis were almost always paired. The results suggestthat prolonged exposure to DXM does alter developmental processes inzebrafish. These results may have implications for future studies on thestructural and functional development of the zebrafish nervous system andbehavior.
doi:10.1016/j.ntt.2009.04.057
NBTS54
Monkey models for studies of maternal and child health: When and why?
Deborah RiceMaine Center for Disease Control and Prevention, Augusta, ME, USA
Because of financial considerations, most teratology and developmentalneurotoxicology studies use rodents as the experimental model. However,there are important differences in physiology and reproductive strategybetween rodents and simian primates, including humans. Rats and mice havea reproductive strategy that is characterized by producing a large number ofoffspring in a short time with little investment in each individual. Primatestypically deliver one offspring after a long gestation period and investsubstantial resources in each offspring. These differences may influence theresponse of the maternal-fetal unit. Laboratory rodents are born less maturethan primates. Humans are typical primates in most respects of reproductionand fetal development. An important exception is that the brains of humaninfants are born less mature than other primates (secondarily altricial). Thebrain structure of primates and rodents is different in a number of importantways, which has important implications for the pattern of effects producedby toxicants. Additionally, monkeys are capable of much more complicatedbehaviors than rodents; in some cases, identical procedures can be used inmonkeys and children. Primates, including humans, use vision as a primaryway of perceiving the world, and a large portion of the primate brain isdevoted to visual processing. Rodents rely on olfaction for much of theirinformation about the environment, which makes behavioral testing morechallenging and interpretation less straightforward. The use of monkeys isappropriate when investigation of specific endpoints that differ in a criticaldimension between rodents and primates is desirable.
doi:10.1016/j.ntt.2009.04.058
NBTS55
Nonhuman primate models for pediatric AIDS
Nancy Haigwooda,b, Koen Van RompaycaOregon National Primate Research Center, Beaverton, OR, USAbOregon Health and Sciences University, Beaverton, OR, USAcCalifornia National Primate Research Center, Davis, California, USA
Nonhuman primate (NHP) models for HIV infection and AIDS have beendeveloped and refined over the last 20 years in an effort to investigate keyquestions in lentiviral transmission and pathogenesis. There are an estimatedhalf million HIV-infected children who are born to infected mothers eachyear. Vertical transmission of HIV has been studied extensively, in an effort tounderstand factors contributing to the timing and route of infection, whichcan be in utero, intrapartum, or postpartum via breastmilk. Progress in the
NBTS 2009 Abstracts250