(1 µg/L). We also found changes in the expression of genes critical fordopaminergic development, including DAT (3.4 fold), tyrosinehydroxylase (3.2 fold) and the transcription factors nurr1 (3.3 fold)and pitx3 (3.6 fold) that persist at least up to 2 weeks post exposure.These data validate the zebrafish as a model for studying pyrethroidneurotoxicity.

doi:10.1016/j.ntt.2010.04.025

NBTS25Using zebrafish to investigate persisting cognitive andsensorimotor effects of early developmentalchlorpyrifos exposure

Edward LevinDuke University Medical Center, Durham, NC, United States

Zebrafish provide a valuable complementary model for determin-ing persisting neurobehavioral impacts of early developmentaltoxicant exposure. This vertebrate model covers an important middleground between high throughput cell based assays and classic rodentmodels. Embryonic zebrafish have continuous visual access forinvestigation of toxicant effects on complex cellular interactions overspatial and temporal domains. Critical to the understanding ofneurobehavioral toxicity they can be tested for a variety of behavioralfunctions from simple sensorimotor response to cognitive function. Ina series of studies our lab has investigated the persisting neurobe-havioral effects of developmental exposure of zebrafish to thepesticide chlorpyrifos. Exposure to chlorpyrifos (0.29 µM) duringthe first five days after fertilization caused persistent impairment inlearning and memory. The learning impairment was accompanied bya persisting decrease in brain dopamine concentration, which wehave found to significantly correlate with learning in zebrafish. Thememory impairment was mimicked by morpholino-induced sup-pression of acetylcholinesterase to a similar extent as caused bychlorpyrifos. Developmental chlorpyrifos exposure also increasedlocomotor response to a tactile startle and decreased predatoryescape response in a novel environment. Zebrafish are sensitive to thepersistent behavioral effects of developmental chlorpyrifos and othertoxicants as well. Abundant opportunities exist to use zebrafish todetermine critical cellular and molecular processes underlyingbehavioral toxicity. With high throughput in vitro assays and classicrodent research, zebrafish can provide mechanistic information in abehaving organism to knit together a more integrated understandingof neurobehavioral toxicity. Supported by ES10356.

doi:10.1016/j.ntt.2010.04.026

NBTS26Neurobehavioral development following exposure of male mice topolybrominated diphenyl ether 47 on postnatal day 10

Virginia Mosera, Pamela Phillipsa, Katherine McDaniela, Jill Geea,baUS Environmental Protection Agency, Research Triangle Park, NC,United StatesbNorth Carolina State University, Raleigh, NC, United States

Polybrominated diphenyl ethers (PBDEs) are persistent pollutantsthat were commonly used as commercial flame retardants. Previousstudies in our laboratory and in the literature have shown thatexposure to a specific PBDE congener, PBDE-47, during a critical

period of brain development leads to developmental delays andhyperactivity in adulthood. This study aimed to further evaluatechanges in motor activity as well as learning in a Morris water maze.C57BL/6 mice received PBDE-47 (0, 1, 10, or 30 mg/kg) on postnatalday 10 (n=12 litters/dose), and one male from each litter wasassigned to one of the following behavioral tests: basal activity levels(1, 2, 4 months of age); acute motor activity response to scopolamineor mecamylamine (4 months); or spatial learning in a Morris watermaze (3, 5 months) followed by no-platform and visual probes.Activity levels showed subtle differences in basal levels at 1 monthonly, and slight attenuation of responses to the pharmacologicalchallenges in the low-dose group only. The only dose-related dif-ference in the water maze was a suggestion that the low-dose micespent less time in the middle zone at 5 months. Thus, in this study wewere unable to replicate motor activity changes from our previousstudy, and did not detect marked changes in spatial learning, up to5 months of age following early postnatal exposure to PBDE-47. Smallsample size and procedural differences may have contributed to theoutcomes. This is an abstract of a proposed presentation and does notreflect US EPA policy.

doi:10.1016/j.ntt.2010.04.027

NBTS27Subsequent effects on open-field responses of exposing male andfemale hooded rats each day to alcohol, caffeine andtheir combination during early and mid to late adolescence,and early adulthood

Rob HughesUniversity of Canterbury, Christchurch, New Zealand

Because of increasing preferences for caffeinated alcoholic drinksamongst young people (many of whom are still undergoingadolescent brain development and associated vulnerability to drug-induced changes), male and female rats were injected each day withsaline, alcohol (2 g/kg), caffeine (100 mg/kg) or both (alcohol+caffeine) during early adolescence (Postnatal Days [PND] 30–39), midto late adolescence (PND45–54) or early adulthood (PND60–69).Their adult behavior in an open field was assessed at PND100.Ambulation was decreased by treatment with alcohol+caffeine atPND30 and 45, but not at PND60. Within-session habituation of thisresponse was impaired for males only following treatment withalcohol at PND45, and by caffeine for all rats following treatment atPND60. Rearing was decreased by treatment with alcohol+caffeineat all three ages, and alcohol reduced this response followingtreatment at PND45 and 60, as did caffeine at PND45. Center squaresoccupancy was decreased only for males following treatment withcaffeine at PND30, and increased for all rats by treatment withcaffeine+alcohol at PND45. Depending on the age of treatment andthe sex of the rats, alcohol alone or in combination with caffeineproduced lower activity and possibly less emotional reactivity.Caffeine might have had the opposite effect in males treated atPND30. Alcohol impaired but caffeine facilitated within-sessionhabituation of ambulation (and thus possibly working memory) inmales treated at PND45. But caffeine treatment at PND60 for all ratsimpaired habituation. Overall, it would appear that treatment atPND60 produced fewer subsequent effects than treatment at theother two ages.

doi:10.1016/j.ntt.2010.04.028

NBTS 2010 Abstract 503