bEunice Kennedy Shriver Center on Human Development and Disability,University of Washington, Seattle, WA, USAcMaine Center for Disease Control, Augusta, ME, USA

As rates of certain childhood disabilities rise, there is a growing awarenessthat exposure to toxic chemicals may be contributing to the increased numberof affected children. Whereas human epidemiology research is important forestablishing relationships between chemical exposures and effects, compara-tive work with animals provides a critical link in modeling consequences ofdevelopmental exposure. The traditional endpoint in assessing the develop-mental risks of chemicals has largely been structural malformation in exposedoffspring. Monkeys have shown sensitivity, in terms of structural malforma-tions, to teratogens such as alcohol, androgenic hormones, diethylstilbestrol,anticancer alkylating agents, anticonvulsants and vitamin A analogs. Asmodels of developmental risk have evolved, so has the conceptualization ofwhat constitutes a chemically-induced injury. Contemporary exposurescenarios are frequently characterized by chronic, low-dose exposure andthe absence of clinical neurotoxicity in bothmothers and offspring. Exposure-related effects are likely to originate in the nervous system and be expressed asfunctional losses in behavior and sensory acuity. In the context of nervoussystem development, four environmental chemicals have been examined inlongitudinal studies with monkeys: lead, methylmercury, polychlorinatedbiphenyls and methanol. Key insights from these studies will be explored inthe context of human development, underscoring the complex and sometimesubtle nature of nervous system injury.

doi:10.1016/j.ntt.2009.04.032

NBTS29

Effects of body weight on locomotor activity and auditory startleresponse in neonatal rats

Melissa Beck, Julie Varsho, Donald Stump, Mark NemecWIL Research Laboratories, LLC, Ashland, OH, USA

It is hypothesized that differences in growth rates in control groupsacross studies may impact the population of data in behavioral historicalcontrol, leading to greater variability across the dataset. Given the increasedscrutiny of variability in behavioral datasets by the US EPA, the WILlocomotor activity and auditory startle response historical control databaseswere analyzed to more precisely characterize these relationships. Data wereobtained from Crl:CD(SD) rats tested for activity on PND 13, 17 and 21 usingthe SDI-PAS for a period of 1 h at each interval and on PND 20 using the SDI-SR for a series of 50 trials. Data for each assessment were blocked by bodyweight into 5-g increments for each sex. For PND 13 females, mean activitycounts increased from animals weighing 15–20 g (386 counts) to peak foranimals that weighed 20–25 g (764 counts). Similar trends were noted onPND 17, with mean activity counts peaking for males and females thatweighed 25–30 g (1848 counts for males and 2085 counts for females). Forauditory startle responsivity on PND 20, peak amplitude increased for pupsweighing 20–30 g (50–80 mV) to peak for pups weighing 50–60 g (180–230 mV). In addition, weight differences of approximately 10% weresufficient to cause detectable increases in responsivity. These datademonstrate that weight differences in control groups across studies canimpact the ability to compare study data to historical control data and alsoidentify a factor that impacts on variability within a historical controldataset.

doi:10.1016/j.ntt.2009.04.033

NBTS30

Undernutrition in early life does not impair learning in young oraged animals

Mary Gilbert, Robert MacPhail, J. Baldwon, V.C. Moser, N. ChernoffU.S. Environmental Protection Agency, Research Triangle Park, NC, USA

Reports on the impact of pre- and postnatal undernutrition on cognitivefunction are evident in both epidemiological and animal studies. The presentstudy extended the duration of assessment to include young adult, middleaged and geriatric animals to investigate the potential of early developmentalinsult to exacerbate normal cognitive decline expected with age. Intrauterinegrowth retardation (IUGR) was induced by restricting food in pregnant SDdams to 50% of control intake from GD2 until parturition. Postnatal under-nutritionwas induced by fostering newborns from each group to control damsin large (n=16 pups) or small (n=8 pups) litters, producing 4 treatmentconditions (Con-Con, IUGR-Con, Con-Postnatal Undernutrition, IUGR-Post-natal Undernutrition). Tests ofmotor activity and hippocampal-based learningwere performed in independent groups of animals at 3–4 different ages.Weight reductions were evident in both postnatally-treated groups atweaning and throughout life. Motor activity, especially rearing, was reducedas a function of age, but equally across all treatment groups. Trace fearconditioning was induced by presentation of 2 light/tone-shock pairings andcontext and cue learning assessed the following day. No treatment-relateddifferences were detected, but a clear age-dependent impairment was seen incontext learning. Neither were group-dependent impairments detected inspatial learning as assessed in theMorriswatermaze at 12 or 20months of age.These data suggest that developmental undernutrition does not exacerbatethe degree or onset of cognitive decline that accompanies old age. (Does notreflect EPA policy).

doi:10.1016/j.ntt.2009.04.034

NBTS31

Innovative methodology using computerized touch-sensitive technologyto evaluate learning and memory in infant monkeys

Thomas Burbachera,b, Noelle McKaina,b, Kimberly Granta,b, Dorothy MandellcaDepartment of Environmental and Occupational Health Sciences,University of Washington, Seattle WA, USAbEunice Kennedy Shriver Center on Human Development and Disability,University of Washington, Seattle, WA, USAcWashington National Primate Center, University of Washington, Seattle,WA, USA

To meet the challenges of modern psychometrics, the Infant PrimateResearch Laboratory (IPRL) at the University of Washington has developed acomputerized touch screen testing system to evaluate learning and memory ininfant monkeys. The development of this methodology was based on theprominence of touch screens or joysticks in neurophysiological and behavioralstudies of cognition in humans. The test systemdeveloped at the IPRL can assesslearning and memory in animals as young as 90 days of age. The following testprocedures have been engineered and adapted for use in our laboratory:Discrimination learning, Spatial search, Learning set, Delayed response,Nonmatch-to-Sample, Nonmatch-to-Sample list length, Match-to-Sample, andMatch-to-Sample list length. Results indicate thatmost youngmonkeys are ableto learn these tasks quickly but strong individual differences are revealed in theamount of time that it takes to learn the task as well as in overall performancelevels. With the rise of studies exploring brain-behavior connections acrossspecies, we expect that computer testing with touch sensitive technology willsoon be the gold standard of cognitive testing in animals. Results from ourlaboratory demonstrate the feasibility of using computers to assess cognitiveand perceptual development. This emerging testmethodologywill be avaluabletool for evaluating the neurobehavioral effects of developmental exposure toneurotoxicants in both humans and nonhuman primates.

doi:10.1016/j.ntt.2009.04.035

NBTS32

12 year growth trajectories of children prenatally exposed to cocaine

Lynn Singer, Elizabeth Short, Meeyoung Min, Barbara Lewis, Sonia MinnesCase Western Reserve University, Cleveland, Ohio, USA

NBTS 2009 Abstracts244