- Email: [email protected]
The Barnes maze: A technique for evaluating spatial learning strategies in prenatally treated mice
1997 NBTS ABSTRACTS
reducing both blood and brain Pb levels in a rat Animals model of early childhood Pb exposure. were exposed to Pb from birth until day 40 of life, followed by oral treatment with a vehicle or one of two succimer regimens for a duration of either 7 or 21 days, and then sacrificed. Preliminary results indicate that succimer effectively lowered both brain and blood Pb levels, but that the reductions in blood Pb levels overestimated reductions in brain Pb by a factor of approximately 2. These results indicate that chelation-mediated reductions in brain Pb do not parallel reductions in blood Pb, suggesting that the use of blood Pb level as a surrogate of brain Pb following succimer treatment should be exercised with caution. (Supported by NIEHS #ES07457).
NBTS 49 Livezey, G-T., and C.V. Smith, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE. Characteristics of the newborn EEG as notential teratological markers. Previous animal studies in our laboratory have demonstrated that subtle changes in brain function following prenatal exposure to psychoactive drugs are reflected in the electroencephalogram (EEG) of the adult offspring. We are now recording the EEG of newborn children for the first 24 hours after birth. Our recording techniques are designed to minimize our impact on that precious time for mother and child. In those patients that require internal monitoring, we also add a second fetal scalp electrode to record fetal EEG during labor. We are collecting relevant outcome data, including followup at 2, 5 and 8 years of age in those patients still available to us. To date we have one fetal and eleven newborn datasets with one patient taking phenobarbital.This is a small sampling, however we have begun to analyze the effect of various control factors on the characteristics of the newborn EEG to establish the normative ranges for our control dataset. This will allow us to consider what characteristics of the EEG may serve as biomarkers for neurobehavioral teratological effects. We will describe the salient features derived from our analysis and the normal variations observed thus far. It is our intent to develop a safe and sensitive diagnostic tool for both additional fetal monitoring and for newborn neurological evaluation. This work is supported by the Leland J. and Dorothy H. Olson Center for Women’s Health.
255
NBTS 50 GAZZARA, R.A.* (Presented by R.R. National Center for Toxicological HOLSON). Research, Jefferson, Arkansas. Amphetamineevoked dopamine release in the neostriatum of the developing ---rat: an in vivo microdialysis study. Previously (Gazzara, et al., Dev. Brain Re.s., 28: 213-220, 1986), we showed, (using stearatemodified voltammetry) that d-amphetamine (AMPH) produced a decrease in dopamine (DA) release in the neostriatum of 21-22-day-old rat Recent evidence has questioned the pups. selectivity of these electrodes for DA and so we decided to reinvestigate this effect using in vivo Urethane-anesthetized rat pups microdialysis. (21-22 or 35-36 days of age) and adult rats were in the prepared for in vivo microdialysis neostriatum. After a stable baseline was reached, AMPH (0.1, 1 .O or 5.0 mg/kg) was administered S.C. Ten-minute samples were collected for 3 hr postinjection. AMPH increased DA release at all ages and at all doses, however the magnitude of the effect increased with age. In additional microdialysis experiments, we tested the ability of locally-applied AMPH (0.01-1000 PM) to increase neostriatal DA release in urethane-anesthetized 5Again AMPH day-old pups and adult rats. increased DA release at both ages, however the maximum effect was larger, and the minimum effective concentration was lower, in the adult rats. Thus, AMPH can evoke neostriatal DA release in vivo in rats as young as 5 days of age, but its effectiveness increases with age.
NBTS 51 INMAN, S.L., L.L. MORFORD*, and C.V. VORHEES, Div. of Dev. Biol., Children’s Hosp. Res. Foundation & Univ. of Cincinnati, Cincinnati, Ohio. The Barnes Maze: A technique for evaluatina spatial learning strategies in prenatally treated mice. The purpose of this study was to evaluate the Barnes maze for its ability to assess spatial learning and memory in prenatally cocaine treated mice. The Barnes maze is a white disc 122 cm in diameter with 40 5cm holes, evenly spaced around the perimeter. The mouse must learn and remember the relationship among distal cues to navigate to an
256 escape tunnel located beneath one of the holes. Each session begins after 10 sec. when a start chamber is lifted and the number of errors and latency to the first hole and the goal are recorded. Mice receive 1 trial/day (limit 4 min.) to a criterion of 718 days with 3 or fewer errors to a limit of 45 days. Conceptually, the Barnes maze is similar to the Morris maze, but it has been reported to have several advantages. The Barnes maze is physically less taxing, is easily transversed by both young and old animals, and most importantly reveals strategies used during acquisition of the task. In a preliminary experiment, we evaluated the feasibility of using the Barnes maze in mice prenatally treated with cocaine. The data indicate that CF-1 mice treated with cocaine (20 mg/kg, twice daily) on embryonic (E) days E8-18 show deficits in overall learning in the Barnes maze. Data on strategies to solve this task will be presented. (Supported by NIH grants ES07051 and DA06733)
NBTS 52 E.D. LEVIN., Departments of Psychiatry and Pharmacology, Duke University Medical Center, . . Durham, North Carolina. m NICK
Maternal smoking during pregnancy can cause persistent cognitive impairments. Variability in the expression of the adverse functional effects may be due to converging risk factors. Prenatal nicotine has the potential to impair neuroplasticity normally seen during development. In rats and humans, the developing frontal cortex is very plastic and substantial functional recovery can occur after neonatal frontal cortical damage. This recovery is dependent on the integrity of norepinepherine (NE) systems. NE response has been found in our studies to be substantially compromised by prenatal nicotine exposure. Prenatal nicotine administration in SpragueDawley rats (2 mg/kg/day GDI-birth) significantly decreases cortical NJ5 levels, and essentially eliminates the ability of acute nicotine to elicit NE release. Subsensitivity of NE systems is also seen with regard to cognitive function. Radial-arm maze memory deficits can be induced in control rats by either the alpha-adrenergic agonist phenylpropanolamine or the betaadrenergic antagonist propranolol. Prenatal nicotine eliminates significant response to either phenylpropanolamine or propranolol. The under-
1997 NBTS ABSTRACTS
responsivity of NE systems after prenatal nicotine exposure may impair the ability of the offspring to recover from frontal cortical trauma during and after birth. ln this way prenatal nicotine exposure may predispose the offspring to lasting deficits after neonatal frontal cortical damage.
NBTS 53 KODITUWAKKU, P. W. ,Department of Psychiatry, University of New Mexico. Albuquerque, New Mexico. Executive control functionine alcohol in utero. We investigated executive control functioning in children with Fetal Alcohol Syndrome (FAS), utilizing a “two-system” model. According to this model executive control functioning is mediated through two systems: one dedicated to the processing of emotionally more relevant information (system A), and the other dedicated to the processing of emotionally less relevant information (system B). We have reported that children with FAS performed more poorly than normal controls on a number of tasks that purport to measure the integrity of system B. Specifically, children with FAS showed a greater difficulty than normal controls on those complex tasks that involve the manipulation of information in working memory. Our current research focuses on abilities that are believed to be mediated through system A (.e.g., delay of gratification and social perspective taking). Dissociation of functions mediated through the two systems will be discussed.
NBTS 54 HANS, S.L., Department of Psychiatry, The University of Chicago, Chicago, Illinois. Effects of Prenatal Exposure to Opiates on Attention during Middle Childhood. Attention was assessed using the Continuous Performance Test (CPT) in a sample of thirty-six ten-year-old
reducing both blood and brain Pb levels in a rat Animals model of early childhood Pb exposure. were exposed to Pb from birth until day 40 of life, followed by oral treatment with a vehicle or one of two succimer regimens for a duration of either 7 or 21 days, and then sacrificed. Preliminary results indicate that succimer effectively lowered both brain and blood Pb levels, but that the reductions in blood Pb levels overestimated reductions in brain Pb by a factor of approximately 2. These results indicate that chelation-mediated reductions in brain Pb do not parallel reductions in blood Pb, suggesting that the use of blood Pb level as a surrogate of brain Pb following succimer treatment should be exercised with caution. (Supported by NIEHS #ES07457).
NBTS 49 Livezey, G-T., and C.V. Smith, Department of Obstetrics and Gynecology, University of Nebraska Medical Center, Omaha, NE. Characteristics of the newborn EEG as notential teratological markers. Previous animal studies in our laboratory have demonstrated that subtle changes in brain function following prenatal exposure to psychoactive drugs are reflected in the electroencephalogram (EEG) of the adult offspring. We are now recording the EEG of newborn children for the first 24 hours after birth. Our recording techniques are designed to minimize our impact on that precious time for mother and child. In those patients that require internal monitoring, we also add a second fetal scalp electrode to record fetal EEG during labor. We are collecting relevant outcome data, including followup at 2, 5 and 8 years of age in those patients still available to us. To date we have one fetal and eleven newborn datasets with one patient taking phenobarbital.This is a small sampling, however we have begun to analyze the effect of various control factors on the characteristics of the newborn EEG to establish the normative ranges for our control dataset. This will allow us to consider what characteristics of the EEG may serve as biomarkers for neurobehavioral teratological effects. We will describe the salient features derived from our analysis and the normal variations observed thus far. It is our intent to develop a safe and sensitive diagnostic tool for both additional fetal monitoring and for newborn neurological evaluation. This work is supported by the Leland J. and Dorothy H. Olson Center for Women’s Health.
255
NBTS 50 GAZZARA, R.A.* (Presented by R.R. National Center for Toxicological HOLSON). Research, Jefferson, Arkansas. Amphetamineevoked dopamine release in the neostriatum of the developing ---rat: an in vivo microdialysis study. Previously (Gazzara, et al., Dev. Brain Re.s., 28: 213-220, 1986), we showed, (using stearatemodified voltammetry) that d-amphetamine (AMPH) produced a decrease in dopamine (DA) release in the neostriatum of 21-22-day-old rat Recent evidence has questioned the pups. selectivity of these electrodes for DA and so we decided to reinvestigate this effect using in vivo Urethane-anesthetized rat pups microdialysis. (21-22 or 35-36 days of age) and adult rats were in the prepared for in vivo microdialysis neostriatum. After a stable baseline was reached, AMPH (0.1, 1 .O or 5.0 mg/kg) was administered S.C. Ten-minute samples were collected for 3 hr postinjection. AMPH increased DA release at all ages and at all doses, however the magnitude of the effect increased with age. In additional microdialysis experiments, we tested the ability of locally-applied AMPH (0.01-1000 PM) to increase neostriatal DA release in urethane-anesthetized 5Again AMPH day-old pups and adult rats. increased DA release at both ages, however the maximum effect was larger, and the minimum effective concentration was lower, in the adult rats. Thus, AMPH can evoke neostriatal DA release in vivo in rats as young as 5 days of age, but its effectiveness increases with age.
NBTS 51 INMAN, S.L., L.L. MORFORD*, and C.V. VORHEES, Div. of Dev. Biol., Children’s Hosp. Res. Foundation & Univ. of Cincinnati, Cincinnati, Ohio. The Barnes Maze: A technique for evaluatina spatial learning strategies in prenatally treated mice. The purpose of this study was to evaluate the Barnes maze for its ability to assess spatial learning and memory in prenatally cocaine treated mice. The Barnes maze is a white disc 122 cm in diameter with 40 5cm holes, evenly spaced around the perimeter. The mouse must learn and remember the relationship among distal cues to navigate to an
256 escape tunnel located beneath one of the holes. Each session begins after 10 sec. when a start chamber is lifted and the number of errors and latency to the first hole and the goal are recorded. Mice receive 1 trial/day (limit 4 min.) to a criterion of 718 days with 3 or fewer errors to a limit of 45 days. Conceptually, the Barnes maze is similar to the Morris maze, but it has been reported to have several advantages. The Barnes maze is physically less taxing, is easily transversed by both young and old animals, and most importantly reveals strategies used during acquisition of the task. In a preliminary experiment, we evaluated the feasibility of using the Barnes maze in mice prenatally treated with cocaine. The data indicate that CF-1 mice treated with cocaine (20 mg/kg, twice daily) on embryonic (E) days E8-18 show deficits in overall learning in the Barnes maze. Data on strategies to solve this task will be presented. (Supported by NIH grants ES07051 and DA06733)
NBTS 52 E.D. LEVIN., Departments of Psychiatry and Pharmacology, Duke University Medical Center, . . Durham, North Carolina. m NICK
Maternal smoking during pregnancy can cause persistent cognitive impairments. Variability in the expression of the adverse functional effects may be due to converging risk factors. Prenatal nicotine has the potential to impair neuroplasticity normally seen during development. In rats and humans, the developing frontal cortex is very plastic and substantial functional recovery can occur after neonatal frontal cortical damage. This recovery is dependent on the integrity of norepinepherine (NE) systems. NE response has been found in our studies to be substantially compromised by prenatal nicotine exposure. Prenatal nicotine administration in SpragueDawley rats (2 mg/kg/day GDI-birth) significantly decreases cortical NJ5 levels, and essentially eliminates the ability of acute nicotine to elicit NE release. Subsensitivity of NE systems is also seen with regard to cognitive function. Radial-arm maze memory deficits can be induced in control rats by either the alpha-adrenergic agonist phenylpropanolamine or the betaadrenergic antagonist propranolol. Prenatal nicotine eliminates significant response to either phenylpropanolamine or propranolol. The under-
1997 NBTS ABSTRACTS
responsivity of NE systems after prenatal nicotine exposure may impair the ability of the offspring to recover from frontal cortical trauma during and after birth. ln this way prenatal nicotine exposure may predispose the offspring to lasting deficits after neonatal frontal cortical damage.
NBTS 53 KODITUWAKKU, P. W. ,Department of Psychiatry, University of New Mexico. Albuquerque, New Mexico. Executive control functionine alcohol in utero. We investigated executive control functioning in children with Fetal Alcohol Syndrome (FAS), utilizing a “two-system” model. According to this model executive control functioning is mediated through two systems: one dedicated to the processing of emotionally more relevant information (system A), and the other dedicated to the processing of emotionally less relevant information (system B). We have reported that children with FAS performed more poorly than normal controls on a number of tasks that purport to measure the integrity of system B. Specifically, children with FAS showed a greater difficulty than normal controls on those complex tasks that involve the manipulation of information in working memory. Our current research focuses on abilities that are believed to be mediated through system A (.e.g., delay of gratification and social perspective taking). Dissociation of functions mediated through the two systems will be discussed.
NBTS 54 HANS, S.L., Department of Psychiatry, The University of Chicago, Chicago, Illinois. Effects of Prenatal Exposure to Opiates on Attention during Middle Childhood. Attention was assessed using the Continuous Performance Test (CPT) in a sample of thirty-six ten-year-old