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Early life and lifelong oral manganese exposure impairs visual attention but not impulse control in adult rats
NBTS 2013 Abstracts
activity differences in either sex during the baseline period. Acute MPH treatment increased activity to a similar extent in males regardless of prior developmental treatment. However, the locomotor activity of females that had been developmentally treated with low MPH was significantly attenuated after acute MPH treatment relative to control females. Thus, developmental MPH treatment appears to have sex- and age-specific effects. Males exhibited hypoactivity during adolescence which appeared to normalize by adulthood. Females exhibited no adolescent activity alterations, but were less responsive to the locomotor-stimulating effects of MPH at adulthood. These results with others forthcoming from this comprehensive study will provide data that are greatly needed for risk assessment of MPH use during pregnancy. (Supported by NCTR Experiment 7318.) http://dx.doi.org/10.1016/j.ntt.2013.03.027
NBTS 25 Prenatal marijuana exposure predicts marijuana use in offspring during young adulthood Kristen Sonona, Nancy Daya,b, Gale Richardsona,b a Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA b Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA Prenatal marijuana exposure (PME) disrupts the developing CNS. This has been observed as behavioral problems in early childhood through adulthood. Studies have demonstrated that PME is a significant predictor of initiation and use during adolescence and young adulthood (Day et al., 2006; Porath and Fried, 2005). We will evaluate the effect of PME on frequency of marijuana use in offspring at 22 years of age. Women were recruited from a prenatal clinic in Pittsburgh, Pennsylvania from 1982 to 1985. Women were in their fourth month of pregnancy. The birth cohort was 763 live singleton infants. On average, the mothers were 23 years old (range: 18–42) and completed 12 years of education (range: 7–18). Half of the women were African American (52%) and half were Caucasian (48%). Women were of low socioeconomic status with approximately 60% reporting a monthly household income of <$400. Forty-eight percent of the offspring were male. Women were assessed at the end of each trimester of pregnancy, and with their offspring, at birth, 8 and 18 months, and at 3, 6, 10, 14,16, and 22 years. Growth and psychosocial, environmental, and behavioral factors were assessed at each phase. At 22 years, frequency of offspring marijuana use was defined as no use, non-regular use (<3 times/week), and regular use (≥3 times/week). Using an ordinal logistic regression model, analyses were performed on 608 mother–offspring pairs, representing 80% of the birth cohort. PME significantly predicted frequency of use in offspring at 22 years, suggesting that the odds of higher frequency of use increased as PME increased. These findings remained significant controlling for maternal and offspring substance use, psychosocial variables, family history of problematic substance use, and factors in the home environment. Offspring exposed to PME used marijuana more frequently as young adults, and this finding remained significant after controlling for familial and environmental influences. We conclude that PME is a significant predictor of offspring marijuana use in early adulthood. Day NL, Goldschmidt L, Thomas CA. Prenatal marijuana exposure contributes to the prediction of marijuana use at age 14. Addiction 2006;101(9):1313–22. Porath AJ, Fried PA. Effects of prenatal cigarette and marijuana exposure on drug use among offspring. Neurotoxicol Teratol 2005;27(2):267–77. http://dx.doi.org/10.1016/j.ntt.2013.03.028
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NBTS 26 Early life and lifelong oral manganese exposure impairs visual attention but not impulse control in adult rats Stephane Beaudina, Myra Strawdermanb, Barbara Struppb, Don Smitha a University of California, Santa Cruz, Santa Cruz, USA b Cornell University, Ithaca, USA Overexposure to manganese (Mn) in early life is link to attention deficit with hyperactivity disorder (ADHD) in children, but this observation has not been tested experimentally in a pre-clinical model. The aim of this study was twofold: (1) determine whether early life Mn exposed rats exhibited persistent deficits in visual attentional processes and impulsive behavior in adulthood, and (2) determine if lifelong Mn exposure caused similar or more severe attention disorder than early life exposure alone. A total of 115 neonates were orally exposed to 0, 25 or 50 mg Mn/kg/d over PND 1–21 only or from PND 1–throughout life. Cognitive testing occurred over four months using the 5-choice serial reaction time task (5-CSRTT) with or without olfactory distracters. Blood and brain tissue Mn levels were determined by ICP-MS in PND 24 and PND 66 littermates, and at PND ~400 in the behaviorally tested animals. As adults and throughout testing blood and brain Mn levels were not measurably different in the early life Mn-exposed animals than controls, while in the lifelong Mnexposed groups blood Mn levels were only slightly elevated (e.g., ~15 ng/ mL) compared to controls (~8 ng/mL). The Mn-exposed groups showed normal visual attention performance in vigilance tasks, except for the lifelong 50 mg Mn/kg/d which displayed poorer performance than controls when required to wait over long periods of time. However, the Mn-exposed groups displayed impairment in attentional accuracy when required to attend selectively to brief visual cues in the presence of olfactory distracters. Notably, impulse control was not measurably impaired in the Mn groups even under testing conditions that increased responding before visual cue onset. The results provide the first evidence that developmental Mn exposure can cause selective attentional deficit across a range of doses and durations of exposure, including persistent susceptibility to greater distractibility in adulthood. The results are consistent with evidence of dopamine dysfunction of the fronto-striatal neuronal circuit in young and adult rodents treated similarly early in life with Mn, but are not entirely in line with the notion that developmental Mn exposure causes ADHD-like behavior in adult animals. Supported by NIEHS R01ES018990. http://dx.doi.org/10.1016/j.ntt.2013.03.029
NBTS 27 Neurobehavioral evaluations of rats gestationally exposed to gasoline vapors Virginia Moser, Katherine McDaniel, Tracey Beasley, Philip Bushnell Toxicology Assessment Division, NHEERL, U.S. Environmental Protection Agency, RTP, NC, USA As the US fuel supply is moving towards blends with higher ethanol levels, there are questions regarding effects of these fuel vapors in the developing fetus. As part of a project evaluating gasoline–ethanol blends of different proportions, we included an evaluation of inhaled pure gasoline vapor (no ethanol). Pregnant Long–Evans rats (n = 18/concentration) were exposed to gasoline vapors (0, 3000, 6000, 9000 ppm total hydrocarbons) for 6 h/day in whole-body inhalation chambers from gestational days 9 to 20. An additional group (cage controls, n = 12) was included to evaluate the influence of inhalation chamber housing during pregnancy. After birth, offspring were allocated to various neurological, immunological, and metabolic tests. In the present study, one male and one female from each of ten litters per treatment group were used for
activity differences in either sex during the baseline period. Acute MPH treatment increased activity to a similar extent in males regardless of prior developmental treatment. However, the locomotor activity of females that had been developmentally treated with low MPH was significantly attenuated after acute MPH treatment relative to control females. Thus, developmental MPH treatment appears to have sex- and age-specific effects. Males exhibited hypoactivity during adolescence which appeared to normalize by adulthood. Females exhibited no adolescent activity alterations, but were less responsive to the locomotor-stimulating effects of MPH at adulthood. These results with others forthcoming from this comprehensive study will provide data that are greatly needed for risk assessment of MPH use during pregnancy. (Supported by NCTR Experiment 7318.) http://dx.doi.org/10.1016/j.ntt.2013.03.027
NBTS 25 Prenatal marijuana exposure predicts marijuana use in offspring during young adulthood Kristen Sonona, Nancy Daya,b, Gale Richardsona,b a Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA b Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA Prenatal marijuana exposure (PME) disrupts the developing CNS. This has been observed as behavioral problems in early childhood through adulthood. Studies have demonstrated that PME is a significant predictor of initiation and use during adolescence and young adulthood (Day et al., 2006; Porath and Fried, 2005). We will evaluate the effect of PME on frequency of marijuana use in offspring at 22 years of age. Women were recruited from a prenatal clinic in Pittsburgh, Pennsylvania from 1982 to 1985. Women were in their fourth month of pregnancy. The birth cohort was 763 live singleton infants. On average, the mothers were 23 years old (range: 18–42) and completed 12 years of education (range: 7–18). Half of the women were African American (52%) and half were Caucasian (48%). Women were of low socioeconomic status with approximately 60% reporting a monthly household income of <$400. Forty-eight percent of the offspring were male. Women were assessed at the end of each trimester of pregnancy, and with their offspring, at birth, 8 and 18 months, and at 3, 6, 10, 14,16, and 22 years. Growth and psychosocial, environmental, and behavioral factors were assessed at each phase. At 22 years, frequency of offspring marijuana use was defined as no use, non-regular use (<3 times/week), and regular use (≥3 times/week). Using an ordinal logistic regression model, analyses were performed on 608 mother–offspring pairs, representing 80% of the birth cohort. PME significantly predicted frequency of use in offspring at 22 years, suggesting that the odds of higher frequency of use increased as PME increased. These findings remained significant controlling for maternal and offspring substance use, psychosocial variables, family history of problematic substance use, and factors in the home environment. Offspring exposed to PME used marijuana more frequently as young adults, and this finding remained significant after controlling for familial and environmental influences. We conclude that PME is a significant predictor of offspring marijuana use in early adulthood. Day NL, Goldschmidt L, Thomas CA. Prenatal marijuana exposure contributes to the prediction of marijuana use at age 14. Addiction 2006;101(9):1313–22. Porath AJ, Fried PA. Effects of prenatal cigarette and marijuana exposure on drug use among offspring. Neurotoxicol Teratol 2005;27(2):267–77. http://dx.doi.org/10.1016/j.ntt.2013.03.028
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NBTS 26 Early life and lifelong oral manganese exposure impairs visual attention but not impulse control in adult rats Stephane Beaudina, Myra Strawdermanb, Barbara Struppb, Don Smitha a University of California, Santa Cruz, Santa Cruz, USA b Cornell University, Ithaca, USA Overexposure to manganese (Mn) in early life is link to attention deficit with hyperactivity disorder (ADHD) in children, but this observation has not been tested experimentally in a pre-clinical model. The aim of this study was twofold: (1) determine whether early life Mn exposed rats exhibited persistent deficits in visual attentional processes and impulsive behavior in adulthood, and (2) determine if lifelong Mn exposure caused similar or more severe attention disorder than early life exposure alone. A total of 115 neonates were orally exposed to 0, 25 or 50 mg Mn/kg/d over PND 1–21 only or from PND 1–throughout life. Cognitive testing occurred over four months using the 5-choice serial reaction time task (5-CSRTT) with or without olfactory distracters. Blood and brain tissue Mn levels were determined by ICP-MS in PND 24 and PND 66 littermates, and at PND ~400 in the behaviorally tested animals. As adults and throughout testing blood and brain Mn levels were not measurably different in the early life Mn-exposed animals than controls, while in the lifelong Mnexposed groups blood Mn levels were only slightly elevated (e.g., ~15 ng/ mL) compared to controls (~8 ng/mL). The Mn-exposed groups showed normal visual attention performance in vigilance tasks, except for the lifelong 50 mg Mn/kg/d which displayed poorer performance than controls when required to wait over long periods of time. However, the Mn-exposed groups displayed impairment in attentional accuracy when required to attend selectively to brief visual cues in the presence of olfactory distracters. Notably, impulse control was not measurably impaired in the Mn groups even under testing conditions that increased responding before visual cue onset. The results provide the first evidence that developmental Mn exposure can cause selective attentional deficit across a range of doses and durations of exposure, including persistent susceptibility to greater distractibility in adulthood. The results are consistent with evidence of dopamine dysfunction of the fronto-striatal neuronal circuit in young and adult rodents treated similarly early in life with Mn, but are not entirely in line with the notion that developmental Mn exposure causes ADHD-like behavior in adult animals. Supported by NIEHS R01ES018990. http://dx.doi.org/10.1016/j.ntt.2013.03.029
NBTS 27 Neurobehavioral evaluations of rats gestationally exposed to gasoline vapors Virginia Moser, Katherine McDaniel, Tracey Beasley, Philip Bushnell Toxicology Assessment Division, NHEERL, U.S. Environmental Protection Agency, RTP, NC, USA As the US fuel supply is moving towards blends with higher ethanol levels, there are questions regarding effects of these fuel vapors in the developing fetus. As part of a project evaluating gasoline–ethanol blends of different proportions, we included an evaluation of inhaled pure gasoline vapor (no ethanol). Pregnant Long–Evans rats (n = 18/concentration) were exposed to gasoline vapors (0, 3000, 6000, 9000 ppm total hydrocarbons) for 6 h/day in whole-body inhalation chambers from gestational days 9 to 20. An additional group (cage controls, n = 12) was included to evaluate the influence of inhalation chamber housing during pregnancy. After birth, offspring were allocated to various neurological, immunological, and metabolic tests. In the present study, one male and one female from each of ten litters per treatment group were used for