Connecting science and people for better policy

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tected against the behavioral and serotonergic neurotoxic effects of a subsequent MDMA binge. Similar results have been reported for the dopamine (DA) neurotoxin methamphetamine (METH). The present study tested the hypothesis that intermittent adolescent MDMA exposure would protect against the DA neurotoxic effects of a METH binge. Male SpragueDawley rats were injected s.c. with MDMA (10 mg/kg ×2; 4 h interdose interval) or saline every fifth day from postnatal day (PD) 35 through PD 60. The animals were then challenged with either a low- or high-dose METH binge (4 or 8 mg/ kg × 4; 2 h interdose interval) or saline on PD 67. Activity was measured 1 day after the binge, and regional serotonin transporter (SERT) and dopamine transporter (DAT) expression were analyzed at PD 74 by radioligand binding. All animals treated with METH on the challenge day became hyperthermic, independent of pretreatment conditions. Both MDMA-pretreated and drug- naïve rats also showed a dose-dependent hypoactivity 24 h after the first dose of the METH binge. The SERT binding results indicated that adolescent pretreatment with MDMA provided full or partial protection (depending on the brain region) against the serotonergic deficits produced by METH in previously drug-naïve animals. In contrast, MDMA pretreatment failed to protect against METH-induced decreases in striatal DAT binding. These results suggest that the neuroprotective effects of adolescent MDMA pretreatment are confined to the serotonergic system, possibly reflecting a selective upregulation of antioxidant mechanisms in that system. doi:10.1016/j.ntt.2009.04.051 NBTS48 Using litter as the unit of analysis: Where do we stand? R. Robert Holson New Mexico Tech, Socorro, NM, USA Standard statistical texts warn that violation of the assumption of independence is one of the worst of statistical sins, but then do almost nothing to help understand how such violations occur, or what their effects might be. One of the most common and serious of such violations is failure to use the litter as the statistical unit of analysis. l will demonstrate that such violations can have major effects on nominal alpha levels, due to litter effects. Such effects can be measured by within-litter correlations, and I will show how such correlations can either inflate or deflate alpha, depending on details of litter intercorrelations. I will then review four fields of research in behavioral teratology (rodent models of fetal alcohol syndrome, PKU, gestational radiation damage to brain and hypothyroidism). The bulk of the literature in all four of these areas has failed, and continues to fail to use litter as the unit of analysis. I will conclude by discussing what this means for the validity of the research effort into rodent models of human developmental disorders. doi:10.1016/j.ntt.2009.04.052 NBTS49 Connecting science and people for better policy Steven Gilbert, Sean Foley Institute of Neurotoxicology and Neurological Disorders, Seattle, WA, USA Creating responsible public health policies requires not only the best scientific information but also a perspective and societal context for the issue. Toxicological research provides a seemingly overwhelming amount of information, but the discipline has struggled to harness information technology to convey its significance to the public. New web based tools, sometimes called Web 2.0, are making it easier to share and access information and ultimately to place it in a current and historical context. Recent advances in this area include Toxipedia (www.toxipedia.org), a wiki- site concept that is designed to encourage neurotoxicology specialists and public health professionals to share their knowledge. The goal of Toxipedia is to be a definitive, yet accessible, information resource on the hazards and history of chemical and physical agents, regulatory requirements, and risk management. Toxipedia has steadily built content, partnerships, and even incorporated existing projects into its purview. For example, the global toxicological resource center the World Library of Toxicology (www.wltox. org), originally developed by the National Libraries of Medicine is now being managed by Toxipedia. The WLT is designed to encourage toxicologist from around the world to share country specific information. Toxipedia, in conjunction with other partners, recently launched its new integrated pest management resource center IPMopedia (www.ipmopedia.org) to encourage sustainable gardening practices. This session will examine wiki-based technology, Toxipedia, and how the neurotoxicology community can use these sites to share knowledge and make better use of information technology to promote science to shape a healthier and more sustainable world. doi:10.1016/j.ntt.2009.04.053 NBTS50 Self-report behavioral outcomes of 12-year-old cocaine-exposed children Sonia Minnes, Lynn Singer, Meeyoung Min, Cintia Ramos, Sudtida Satayathum Case Western Reserve University, Cleveland, OH, USA Prenatal cocaine exposure may have persistent effects on childhood behavior due to potential disturbances of the monoaminergic neurotrans- mitter systems. Subjects were primarily African American, low socio- economic status, 12 year old children (n =339, 173 cocaine exposed (CE) and 166 non-exposed (NCE). The Youth Self-Report (YSR) was used to assess behavior problems. Behavior profiles for broadband measures (Externalizing, Internalizing and Total) and narrow band subscales (anxious/depressed, withdrawn/depressed, somatic complaints, social problems, thought pro- blems, attention problems, delinquency and aggressive behavior) are provided. Multiple and logistic regressions were used to examine the effect of cocaine on behavior while controlling for covariates including home environment, maternal substance use, and lead exposure. Logistic regression revealed that CE children were 2× more likely to exhibit externalizing problems (OR=2.40; 95% CI: 1.125.13, p = 0.02) in the clinical range after controlling for home environment and current caregiver psychological distress. There was also a significant cocaine by gender interaction effect (p = 0.009), indicating increased odds for externalizing behavior problems for CE females compared to NCE females (OR=5.13; 95% CI: 1.814.3; p = .002). There were no cocaine effects on the YSR mean scores. Greater current caregiver psychological distress was related to more self-reported behavior problems. Findings indicate the importance of early assessment and intervention to reduce behavior problems and risk of substance use among prenatally cocaine-exposed children. doi:10.1016/j.ntt.2009.04.054 NBTS51 Attention and working memory in children exposed prenatally to anticonvulsant monotherapy Patricia Janulewicz a , Jessica Walsh a , Tanya Nixon a , Sam Olson a , Lewis Holmes b , Jane Adams a a University of Massachusetts, Boston, MA, USA b MassGeneral Hospital for Children, Boston, MA, USA While anticonvulsant polytherapy is known to cause structural and functional teratogenicity, the effects of monotherapy are less clear (Adams et al., 2007). Between 1996 and 2006, we examined the effects of prenatal monotherapy with Carbamazepine (CBZ), Phenobarbital (PB), or Phenytoin (PHT) upon the dysmorphological and neuropsychological characteristics of 616 year old children born to women under treatment for seizure disorders compared to demographically-matched non-exposed children (n =3440/ group). The neuropsychological testing battery incorporated several evalua- NBTS 2009 Abstracts 249

Transcript of Connecting science and people for better policy

Page 1: Connecting science and people for better policy

tected against the behavioral and serotonergic neurotoxic effects of asubsequentMDMAbinge. Similar results have been reported for the dopamine(DA) neurotoxin methamphetamine (METH). The present study tested thehypothesis that intermittent adolescent MDMA exposure would protectagainst the DA neurotoxic effects of a METH binge. Male Sprague–Dawleyrats were injected s.c. with MDMA (10 mg/kg×2; 4 h interdose interval) orsaline every fifth day from postnatal day (PD) 35 through PD 60. The animalswere then challengedwith either a low- or high-dose METH binge (4 or 8mg/kg×4; 2 h interdose interval) or saline on PD 67. Activity was measured 1 dayafter the binge, and regional serotonin transporter (SERT) and dopaminetransporter (DAT) expression were analyzed at PD 74 by radioligand binding.All animals treated with METH on the challenge day became hyperthermic,independent of pretreatment conditions. Both MDMA-pretreated and drug-naïve rats also showed a dose-dependent hypoactivity 24 h after the first doseof the METH binge. The SERT binding results indicated that adolescentpretreatment with MDMA provided full or partial protection (depending onthe brain region) against the serotonergic deficits produced by METH inpreviously drug-naïve animals. In contrast, MDMA pretreatment failed toprotect against METH-induced decreases in striatal DAT binding. These resultssuggest that the neuroprotective effects of adolescent MDMA pretreatmentare confined to the serotonergic system, possibly reflecting a selectiveupregulation of antioxidant mechanisms in that system.

doi:10.1016/j.ntt.2009.04.051

NBTS48

Using litter as the unit of analysis: Where do we stand?

R. Robert HolsonNew Mexico Tech, Socorro, NM, USA

Standard statistical texts warn that violation of the assumption ofindependence is one of the worst of statistical sins, but then do almostnothing to help understand how such violations occur, or what their effectsmight be. One of the most common and serious of such violations is failure touse the litter as the statistical unit of analysis. l will demonstrate that suchviolations can have major effects on nominal alpha levels, due to litter effects.Such effects can bemeasured bywithin-litter correlations, and Iwill showhowsuch correlations can either inflate or deflate alpha, depending on details oflitter intercorrelations. I will then review four fields of research in behavioralteratology (rodent models of fetal alcohol syndrome, PKU, gestationalradiation damage to brain and hypothyroidism). The bulk of the literature inall four of these areas has failed, and continues to fail to use litter as the unit ofanalysis. I will conclude by discussing what this means for the validity of theresearch effort into rodent models of human developmental disorders.

doi:10.1016/j.ntt.2009.04.052

NBTS49

Connecting science and people for better policy

Steven Gilbert, Sean FoleyInstitute of Neurotoxicology and Neurological Disorders, Seattle, WA, USA

Creating responsible public health policies requires not only the bestscientific information but also a perspective and societal context for theissue. Toxicological research provides a seemingly overwhelming amount ofinformation, but the discipline has struggled to harness informationtechnology to convey its significance to the public. New web based tools,sometimes called Web 2.0, are making it easier to share and accessinformation and ultimately to place it in a current and historical context.Recent advances in this area include Toxipedia (www.toxipedia.org), a wiki-site concept that is designed to encourage neurotoxicology specialists andpublic health professionals to share their knowledge. The goal of Toxipedia isto be a definitive, yet accessible, information resource on the hazards andhistory of chemical and physical agents, regulatory requirements, and risk

management. Toxipedia has steadily built content, partnerships, and evenincorporated existing projects into its purview. For example, the globaltoxicological resource center the World Library of Toxicology (www.wltox.org), originally developed by the National Libraries of Medicine is now beingmanaged by Toxipedia. The WLT is designed to encourage toxicologist fromaround the world to share country specific information. Toxipedia, inconjunction with other partners, recently launched its new integrated pestmanagement resource center IPMopedia (www.ipmopedia.org) to encouragesustainable gardening practices. This session will examine wiki-basedtechnology, Toxipedia, and how the neurotoxicology community can usethese sites to share knowledge and make better use of informationtechnology to promote science to shape a healthier and more sustainableworld.

doi:10.1016/j.ntt.2009.04.053

NBTS50

Self-report behavioral outcomes of 12-year-old cocaine-exposed children

Sonia Minnes, Lynn Singer, Meeyoung Min, Cintia Ramos,Sudtida SatayathumCase Western Reserve University, Cleveland, OH, USA

Prenatal cocaine exposure may have persistent effects on childhoodbehavior due to potential disturbances of the monoaminergic neurotrans-mitter systems. Subjects were primarily African American, low socio-economic status, 12 year old children (n=339, 173 cocaine exposed (CE)and 166 non-exposed (NCE). The Youth Self-Report (YSR) was used to assessbehavior problems. Behavior profiles for broadband measures (Externalizing,Internalizing and Total) and narrow band subscales (anxious/depressed,withdrawn/depressed, somatic complaints, social problems, thought pro-blems, attention problems, delinquency and aggressive behavior) areprovided. Multiple and logistic regressions were used to examine the effectof cocaine on behavior while controlling for covariates including homeenvironment, maternal substance use, and lead exposure. Logistic regressionrevealed that CE children were 2× more likely to exhibit externalizingproblems (OR=2.40; 95% CI: 1.12–5.13, p=0.02) in the clinical range aftercontrolling for home environment and current caregiver psychologicaldistress. There was also a significant cocaine by gender interaction effect(p=0.009), indicating increased odds for externalizing behavior problemsfor CE females compared to NCE females (OR=5.13; 95% CI: 1.8–14.3;p=.002). There were no cocaine effects on the YSR mean scores. Greatercurrent caregiver psychological distress was related to more self-reportedbehavior problems. Findings indicate the importance of early assessment andintervention to reduce behavior problems and risk of substance use amongprenatally cocaine-exposed children.

doi:10.1016/j.ntt.2009.04.054

NBTS51

Attention and working memory in children exposed prenatally toanticonvulsant monotherapy

Patricia Janulewicza, Jessica Walsha, Tanya Nixona, Sam Olsona,Lewis Holmesb, Jane AdamsaaUniversity of Massachusetts, Boston, MA, USAbMassGeneral Hospital for Children, Boston, MA, USA

While anticonvulsant polytherapy is known to cause structural andfunctional teratogenicity, the effects of monotherapy are less clear (Adamset al., 2007). Between 1996 and 2006, we examined the effects of prenatalmonotherapy with Carbamazepine (CBZ), Phenobarbital (PB), or Phenytoin(PHT) upon the dysmorphological and neuropsychological characteristics of6–16 year old children born to women under treatment for seizure disorderscompared to demographically-matched non-exposed children (n=34–40/group). The neuropsychological testing battery incorporated several evalua-

NBTS 2009 Abstracts 249