Mary L Schneider

University of Wisconsin–Madison, Madison, Wisconsin, United States

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Publications (55)187.32 Total impact

  • [Show abstract] [Hide abstract] ABSTRACT: We examined the effects of moderate prenatal alcohol exposure and/or prenatal stress exposure on (D1 R) binding in a non human primate model. The dopamine D1 R is involved in executive function, and it may play a role in cognitive behavioral deficits associated with prenatal alcohol and/or stress exposure. Little is known, however, about the effects of prenatal alcohol and/or stress exposure on the D1 R. We expected that prenatal insults would lead to alterations in D1 R binding in prefrontal cortex (PFC) and striatum in adulthood. Rhesus macaque females were randomly assigned to moderate alcohol exposure and/or mild prenatal stress as well as a control condition during pregnancy. Thirty-eight offspring were raised identically and studied as adults by noninvasive in vivo neuroimaging using positron emission tomography with the D1 antagonist radiotracer [(11) C]SCH 23390. Radiotracer binding in PFC and striatum was evaluated by 2 (alcohol) × 2 (stress) × 2 (sex) analysis of variance. In PFC, a significant alcohol × sex interaction was observed with prenatal alcohol exposure leading to increased [(11) C]SCH 23390 binding in male monkeys. No main effect of prenatal alcohol or prenatal stress exposure was observed. These results suggest that prenatal alcohol exposure results in long-term increases in prefrontal dopamine D1 R binding in males. This may help explain gender differences in the prevalence of neurodevelopmental disorders consequent to prenatal alcohol exposure. Copyright © 2015 by the Research Society on Alcoholism.
    No preview · Article · Dec 2014 · Alcoholism Clinical and Experimental Research
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Previous studies have found interrelationships between the serotonin system and alcohol self-administration. The goal of this work was to directly observe in vivo effects of chronic ethanol self-administration on serotonin 5-HT1A receptor binding with [(18)F]mefway PET neuroimaging in rhesus monkeys. Subjects were first imaged alcohol-naïve and again during chronic ethanol self-administration to quantify changes in 5-HT1A receptor binding. Methods: Fourteen rhesus monkey subjects (10.7-12.8 years) underwent baseline [(18)F]mefway PET scans prior to alcohol exposure. Subjects then drank gradually increasing ethanol doses over four months as an induction period, immediately followed by at least nine months ad libidum ethanol access. A post [(18)F]mefway PET scan was acquired during the final three months of ad libidum ethanol self-administration. 5-HT1A receptor binding was assayed with binding potential (BPND) using the cerebellum as a reference region. Changes in 5-HT1A binding during chronic ethanol self-administration were examined. Relationships of binding metrics with daily ethanol self-administration were also assessed. Results: Widespread increases in 5-HT1A binding were observed during chronic ethanol self-administration, independent of the amount of ethanol consumed. A positive correlation between 5-HT1A binding in the raphe nuclei and average daily ethanol self-administration was also observed, indicating that baseline 5-HT1A binding in this region predicted drinking levels. Conclusions: The increase in 5-HT1A binding levels during chronic ethanol self-administration demonstrates an important modulation of the serotonin system due to chronic alcohol exposure. Furthermore, the correlation between 5-HT1A binding in the raphe nuclei and daily ethanol self-administration indicates a relationship between the serotonin system and alcohol self-administration.
    No preview · Article · Aug 2014 · Drug and Alcohol Dependence
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    [Show abstract] [Hide abstract] ABSTRACT: 4-trans-[(18)F]Mefway is a PET radiotracer with high affinity for 5-HT1A receptors. Our preliminary work indicated the positional isomer, 3-[(18)F]mefway, would be suitable for PET imaging of 5-HT1A receptors. We now compare the in vivo behaviour of 3-mefway with 4-mefway to evaluate 3-[(18)F]mefway as a potential 5-HT1A PET radiotracer. Two male rhesus macaques were given bolus injections of both 3- and 4-trans-[(18)F]mefway in separate experiments. 90 minute dynamic PET scans were acquired. TACs were extracted in the mesial temporal lobe (MTL) and caudal anterior cingulate gyrus (cACg). The cerebellum (CB) was used as a reference region. In vivo behavior of the radiotracers in the CB was compared based upon the ratio of normalized PET uptake for 3- and 4-trans-[(18)F]mefway. Specific binding was compared by examining MTL/CB and cACg/CB ratios. The subject-averaged ratio of 3-[(18)F]mefway to 4-trans-[(18)F]mefway in the cerebellum was 0.96 for 60-90 minutes. MTL/CB reached plateaus of ~2.7 and ~6 by 40 minutes and 90 minutes for 3- and 4-trans-[(18)F]mefway, respectively. cACg/CB reached plateaus of ~2.5 and ~6 by 40 minutes and 70 minutes for 3- and 4-trans-[(18)F]mefway, respectively. The short pseudoequilibration times and sufficient uptake of 3-[(18)F]mefway may be useful in studies requiring short scan times. Furthermore, the similar nondisplaceable clearance in the CB to 4-trans-[(18)F]mefway suggests the lower BPND of 3-[(18)F]mefway is due to a lower affinity. The lower affinity of 3-[(18)F]mefway may make it useful for measuring changes in endogenous 5-HT levels, however, this remains to be ascertained.
    Full-text · Article · Aug 2014 · American Journal of Nuclear Medicine and Molecular Imaging
  • [Show abstract] [Hide abstract] ABSTRACT: Background The precise nature of modifications to the nicotinic acetylcholine receptor (nAChR) system in response to chronic ethanol exposure is poorly understood. The present work used PET imaging to assay α4β2* nAChR binding levels of eight rhesus monkeys before and during controlled chronic ethanol intake. Methods [18F]Nifene PET scans were conducted prior to alcohol exposure, and then again after at least 8 months controlled ethanol exposure, including 6 months at 1.5 g/kg/day following a dose escalation period. Receptor binding levels were quantified with binding potentials (BPND) using the cerebellum as a reference region. Alcohol self-administration was assessed as average daily alcohol intake during a 2 month free drinking period immediately following controlled alcohol. Results Significant decreases in α4β2* nAChR binding were observed in both frontal and insular cortex in response to chronic ethanol exposure. During chronic alcohol exposure, BPND in the lateral geniculate region correlated positively with the amount of alcohol consumed during free drinking. Conclusions The observed decreases in nAChR availability following chronic alcohol consumption suggest alterations to this receptor system in response to repeated alcohol administration, making this an important target for further study in alcohol abuse and alcohol and nicotine codependence.
    No preview · Article · May 2014 · Drug and alcohol dependence
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    Full-text · Conference Paper · Sep 2013
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    [Show abstract] [Hide abstract] ABSTRACT: [(18)F]Nifene is an agonist PET radioligand developed to image α4β2* nicotinic acetylcholine receptors (nAChRs). This work aims to quantify the receptor density (Bmax) of α4β2* nAChRs and the in vivo (apparent) dissociation constant (KDapp) of [(18)F]nifene. Multiple-injection [(18)F]nifene experiments with varying cold nifene masses were conducted on four rhesus monkeys with a microPET P4 scanner. Compartment modeling techniques were used to estimate regional Bmax values and a global value of KDapp. The fast kinetic properties of [(18)F]nifene also permitted alternative estimates of Bmax and KDapp at transient equilibrium with the same experimental data using Scatchard-like methodologies. Averaged across subjects, the compartment modeling analysis yielded Bmax values of 4.8±1.4, 4.3±1.0, 1.2±0.4, and 1.2±0.3 pmol/mL in the regions of antereoventral thalamus, lateral geniculate, frontal cortex, and subiculum, respectively. The KDapp of nifene was 2.4±0.3 pmol/mL. The Scatchard analysis based on graphical evaluation of the data after transient equilibrium yielded Bmax estimations comparable to the modeling results with a positive bias of 28%. These findings show the utility of [(18)F]nifene for measuring α4β2* nAChR Bmax in vivo in the rhesus monkey with a single PET experiment.Journal of Cerebral Blood Flow & Metabolism advance online publication, 14 August 2013; doi:10.1038/jcbfm.2013.136.
    Full-text · Article · Aug 2013 · Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Prenatal alcohol exposure can contribute to a wide range of neurodevelopmental impairments in children and adults including behavioral and neuropsychiatric disorders. In rhesus monkeys, we examined whether moderate-level prenatal alcohol exposure would alter acoustic startle responses and prepulse inhibition (PPI) of the acoustic startle. PPI is a highly quantifiable measure of inhibitory neural processes or sensorimotor gating associated with neuropsychiatric disorders. Methods: Acoustic startle and PPI of the acoustic startle were tested in 37 adult rhesus monkeys (Macaca mulatta) from 4 experimental conditions: (i) moderate-level prenatal alcohol-exposed, (ii) prenatally stressed, (iii) moderate-level prenatal alcohol-exposed + prenatally stressed, and (iv) sucrose controls. Results: Prenatal alcohol-exposed monkeys showed a higher magnitude of acoustic startle response and disrupted PPI compared with monkeys not exposed to alcohol prenatally. Monkeys in all conditions showed higher hypothalamic-pituitary-adrenocortical (HPA) axis responses after undergoing the startle procedure, but HPA responses were unrelated to startle response magnitude, latency, or PPI. Conclusions: Finding altered PPI in monkeys prenatally exposed to a moderate dose of alcohol suggests that reduced sensorimotor gating is 1 effect of prenatal alcohol exposure. Because reduced sensorimotor gating is observed in many neuropsychiatric disorders, sensorimotor gating deficits could be an aspect of the comorbidity between fetal alcohol spectrum disorder and mental health conditions.
    No preview · Article · Jun 2013 · Alcoholism Clinical and Experimental Research
  • [Show abstract] [Hide abstract] ABSTRACT: Background: To determine the effects in adult offspring of maternal exposure to stress and alcohol during pregnancy, we imaged striatal and midbrain dopamine transporter (DAT) binding by positron emission tomography in rhesus monkeys (Macaca mulatta). We also evaluated the relationship between DAT binding and behavioral responses previously found to relate to dopamine D2 receptor density (responsivity to tactile stimuli, performance on a learning task, and behavior during a learning task). Methods: Subjects were adult offspring derived from a 2 × 2 experiment in which pregnant monkeys were randomly assigned to control, daily mild stress exposure (acoustic startle), voluntary consumption of moderate-level alcohol, or both daily stress and alcohol. Adult offspring (n = 38) were imaged by positron emission tomography with the DAT ligand [(18)F]2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)-nortropane ([(18)F]FECNT). Results: Results showed that prenatal stress yielded an overall increase of 15% in [(18)F]FECNT binding in the striatum (p = .016), 17% greater binding in the putamen (p = .012), and 13% greater binding in the head of the caudate (p = .028) relative to animals not exposed to prenatal stress. Striatal [(18)F]FECNT binding correlated negatively with habituation to repeated tactile stimulation and positively with tactile responsivity. There were no significant effects of prenatal alcohol exposure on [(18)F]FECNT binding. Conclusions: Maternal exposure to mild daily stress during pregnancy yielded increases in striatal DAT availability that were apparent in adult offspring and were associated with behavioral characteristics reflecting tactile hyperresponsivity, a condition associated with problem behaviors in children.
    No preview · Article · May 2013 · Biological psychiatry
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    [Show abstract] [Hide abstract] ABSTRACT: Unlabelled: Serotonin (5-HT) dysfunction has been implicated in neuropsychiatric illnesses and may play a pivotal role in the differential prevalence of depression between the sexes. Previous PET studies have revealed sex-based differences in 5-HT1A binding potential (BPND). The binding potential is a function of the radioligand-receptor affinity (1/KDapp), and receptor density (Bmax). In this work, we use a multiple-injection (MI) PET protocol and the 5-HT1A receptor antagonist, [(18)F]mefway, to compare sex-based differences of in vivo affinity, Bmax, and BPND in rhesus monkeys. Methods: PET [(18)F]mefway studies were performed on 17 (6m, 11f) rhesus monkeys using a 3-injection protocol that included partial saturation injections of mefway. Compartmental modeling was performed using a model to account for non-tracer doses of mefway for the estimation of KDapp and Bmax. BPND estimates were also acquired from the first injection (high specific activity [(18)F]mefway, 90-minute duration) for comparison using the cerebellum (CB) as a reference region. Regions of interest were selected in 5-HT1A binding regions of the hippocampus (Hp), dorsal anterior cingulate cortex (dACC), amygdala (Am), and raphe nuclei (RN). Results: Female subjects displayed significantly (*p<0.05) lower KDapp in the Hp (-32%), Am (-38%), and RN (-37%). Only the Hp displayed significant differences in Bmax with females having a Bmax of -29% compared to males. Male subjects demonstrated significantly lower BPND measurements in the Am (14%) and RN (29%). Conclusion: These results suggest that the higher BPND values found in females are the result of lower [(18)F]mefway KDapp. Although a more experimentally complex measurement, separate assay of KDapp and Bmax provides a more sensitive measure than BPND to identify the underlying differences between females and males in 5-HT1A function.
    Full-text · Article · Mar 2013 · NeuroImage
  • No preview · Article · Feb 2013 · The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
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    [Show abstract] [Hide abstract] ABSTRACT: Disruption of the serotonin system has been implicated in anxiety and depression and a related genetic variation has been identified that may predispose individuals for these illnesses. The relationship of a functional variation of the serotonin transporter promoter gene (5-HTTLPR) on serotonin transporter binding using in vivo imaging techniques have yielded inconsistent findings when comparing variants for short (s) and long (l) alleles. However, a significant 5-HTTLPR effect on receptor binding at the 5-HT(1A) receptor site has been reported in humans, suggesting the 5-HTTLPR polymorphism may play a role in serotonin (5-HT) function. Rhesus monkeys possess a 5-HTTLPR length polymorphism similar to humans and serve as an excellent model for studying the effects of this orthologous genetic variation on behaviors and neurochemical functions related to the 5-HT system. In this study, PET imaging of [(18)F]mefway was performed on 58 rhesus monkeys (33 l/l, 25 s-carriers) to examine the relation between 5-HT(1A) receptor-specific binding and 5-HTTLPR genotypes. Significantly lower 5-HT(1A) binding was found in s-carrier subjects throughout both cortical brain regions and the raphe nuclei. These results demonstrate that the underlying 5-HT neurochemical system is influenced by this functional polymorphism and illustrate the strong potential for extending the nonhuman primate model into investigating the role of this genetic variant on behavior and gene-environment interactions.
    Full-text · Article · Feb 2013 · The Journal of Neuroscience : The Official Journal of the Society for Neuroscience
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    [Show abstract] [Hide abstract] ABSTRACT: The PET radioligand 2-fluoro-3-[2-((S)-3-pyrrolinyl)methoxy]pyridine ((18)F-nifene) is an α4β2* nicotinic acetylcholine receptor (nAChR) agonist developed to provide accelerated in vivo equilibrium compared with existing α4β2* radioligands. The goal of this work was to analyze the in vivo kinetic properties of (18)F-nifene with both kinetic modeling and graphical analysis techniques. Dynamic PET experiments were performed on 4 rhesus monkeys (female; age range, 9-13 y) using a small-animal PET scanner. Studies began with a high-specific-activity (18)F-nifene injection, followed by a coinjection of (18)F-nifene and unlabeled nifene at 60 min. Sampling of arterial blood with metabolite analysis was performed throughout the experiment to provide a parent radioligand input function. In vivo kinetics were characterized with both a 1-tissue-compartment model (1TCM) and a 2-tissue-compartment model, Logan graphical methods (both with and without blood sampling), and the multilinear reference tissue model. Total distribution volumes and nondisplaceable binding potentials (BP(ND)) were used to compare regional binding of (18)F-nifene. Regions examined include the anteroventral thalamus, lateral geniculate body, frontal cortex, subiculum, and cerebellum. The rapid uptake and binding of (18)F-nifene in nAChR-rich regions of the brain was appropriately modeled using the 1TCM. No evidence for specific binding of (18)F-nifene in the cerebellum was detected on the basis of the coinjection studies, suggesting the suitability of the cerebellum as a reference region. Total distribution volumes in the cerebellum were 6.91 ± 0.61 mL/cm(3). BP(ND) values calculated with the 1TCM were 1.60 ± 0.17, 1.35 ± 0.16, 0.26 ± 0.08, and 0.30 ± 0.07 in the anteroventral thalamus, lateral geniculate body, frontal cortex, and subiculum, respectively. For all brain regions, there was a less than 0.04 absolute difference in the average BP(ND) values calculated with each of the 1TCM, multilinear reference tissue model, and Logan methods. The fast kinetic properties and specific regional binding of (18)F-nifene promote extension of the radioligand into preclinical animal models and human subjects.
    Full-text · Article · Jul 2012 · Journal of Nuclear Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: The goal of this work was to characterize the in-vivo behavior of [(18)F]mefway as a suitable positron emission tomography (PET) radiotracer for the assay of 5-hydroxytryptamine(1A) (5-HT(1A)) receptor density (B(max)). Six rhesus monkeys were studied using a multiple-injection (M-I) protocol consisting of three sequential bolus injections of [(18)F]mefway. Injection times and amounts of unlabeled mefway were optimized for the precise measurement of B(max) and specific binding parameters k(off) and k(on) for estimation of apparent K(D). The PET time series were acquired for 180 minutes with arterial sampling performed throughout. Compartmental analysis using the arterial input function was performed to obtain estimates for K(1), k(2), k(off), B(max), and K(Dapp) in the cerebral cortex and raphe nuclei (RN) using a model that accounted for nontracer doses of mefway. Averaged over subjects, highest binding was seen in the mesial temporal and dorsal anterior cingulate cortices with B(max) values of 42±8 and 36±8 pmol/mL, respectively, and lower values in the superior temporal cortex, RN, and parietal cortex of 24±4, 19±4, and 13±2 pmol/mL, respectively. The K(Dapp) of mefway for the 5-HT(1A) receptor sites was 4.3±1.3 nmol/L. In conclusion, these results show that M-I [(18)F]mefway PET experiments can be used for the in-vivo measurement of 5-HT(1A) receptor density.
    Full-text · Article · Apr 2012 · Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism
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    [Show abstract] [Hide abstract] ABSTRACT: [(18)F]Mefway is a serotonin 5-HT(1A) PET radiotracer with high specificity and favorable in vivo imaging properties. The chemical structure of [(18)F]mefway permits (18)F labeling in either the cis or trans positions at the 4-cyclohexyl site. We have previously reported on the in vivo kinetics of trans-[(18)F]mefway in the nonhuman primate. In this work, we compare the in vivo binding of cis-[(18)F]mefway and trans-[(18)F]mefway to evaluate the properties of cis-[(18)F]mefway for 5-HT(1A) PET imaging. The cis- and trans-[(18)F]mefway tracers were synthesized via nucleophilic substitution with their respective tosyl precursors. Two monkeys (one male, one female) were given bolus injections of both cis- and trans-labeled [(18)F]mefway in separate experiments. Dynamic scans were acquired for 90 min with a microPET P4 scanner. Time-activity curves were extracted in the areas of the mesial temporal cortex (MTC), anterior cingulate gyrus (aCG), insular cortex (IC), raphe nuclei (RN) and cerebellum (CB). The in vivo behavior of the radiotracers was compared based upon the nondisplaceable binding potential (BP(ND)) using the CB as a reference region. Averaged over the two subjects, BP(ND) values were as follows: MTC: 7.7, 0.58; aCG: 4.95, 0.32; IC: 3.27, 0.2; and RN: 3.05, 0.13, for trans-[(18)F]mefway and cis-[(18)F]mefway, respectively. The cis-labeled [(18)F]mefway tracer has low specific binding throughout the 5-HT(1A) regions of the brain compared to trans-[(18)F]mefway, suggesting that the target-to-background binding of cis-[(18)F]mefway may limit its use for in vivo assessment of 5-HT(1A) binding.
    Full-text · Article · Jul 2011 · Nuclear Medicine and Biology
  • Mary L Schneider · Colleen F Moore · Miriam M Adkins
    [Show abstract] [Hide abstract] ABSTRACT: The use of alcohol by women during pregnancy is a continuing problem. In this review the behavioral effects of prenatal alcohol from animal models are described and related to studies of children and adults with FASD. Studies with monkeys and rodents show that prenatal alcohol exposure adversely affects neonatal orienting, attention and motor maturity, as well as activity level, executive function, response inhibition, and sensory processing later in life. The primate moderate dose behavioral findings fill an important gap between human correlational data and rodent mechanistic research. These animal findings are directly translatable to human findings. Moreover, primate studies that manipulated prenatal alcohol exposure and prenatal stress independently show that prenatal stress exacerbates prenatal alcohol-induced behavioral impairments, underscoring the need to consider stress-induced effects in fetal alcohol research. Studies in rodents and primates show long-term effects of prenatal and developmental alcohol exposure on dopamine system functioning, which could underpin the behavioral effects.
    No preview · Article · Jun 2011 · Neuropsychology Review
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    [Show abstract] [Hide abstract] ABSTRACT: Moderate prenatal alcohol exposure can contribute to neurodevelopmental impairments and disrupt several neurotransmitter systems. We examined the timing of moderate level alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and levels of primary serotonin and dopamine (DA) metabolites in cerebrospinal fluid (CSF) in rhesus monkeys. Thirty-two 30-month old rhesus monkeys (Macaca mulatta) from 4 groups of females were assessed: (i) early alcohol-exposed group (n = 9), in which mothers voluntarily consumed 0.6 g/kg/d alcohol solution on gestational days 0 to 50; (ii) middle-to-late gestation alcohol-exposed group (n = 6), mothers consumed 0.6 g/kg/d alcohol solution on gestational days 50 to 135; (iii) a continuous-exposure group (n = 8), mothers consumed 0.6 g/kg/d alcohol solution on gestational days 0 to 135; and (iv) controls (n = 9), mothers consumed an isocaloric control solution on gestational days 0 to 50, 50 to 135, or 0 to 135. Serotonin transporter promoter region allelic variants (homozygous s/s or heterozygous s/l vs. homozygous l/l) were determined. We examined CSF concentrations of the 5-HT and DA metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), respectively, at baseline and 50 hours after separation from cage-mates, when the monkeys were 30 months old. Early- and middle-to-late gestation-alcohol exposed monkeys carrying the short allele had lower concentrations of 5-HIAA in CSF relative to other groups. Concentrations of 5-HIAA in CSF were lower for s allele carriers and increased from baseline relative to pre-separation values, whereas 5-HIAA levels in l/l allele carriers were not affected by separation. Monkeys carrying the short allele had lower basal concentrations of HVA in CSF compared with monkeys homozygous for the long allele. Carrying the s allele of the 5-HT transporter increased the probability of reduced 5-HIAA in early- and middle-to-late gestation alcohol-exposed monkeys and reduced HVA at baseline. These findings that prenatal alcohol exposure altered central 5-HT activity in genetically sensitive monkeys raise questions about whether abnormal serotonin biological pathways could underlie some of the psychiatric disorders reported in fetal alcohol spectrum disorder.
    Full-text · Article · Feb 2011 · Alcoholism Clinical and Experimental Research
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    [Show abstract] [Hide abstract] ABSTRACT: The relative maturity, alertness, and reactivity of an infant at birth are sensitive indices of the neonate's health, the quality of the pregnancy, and the mother's wellbeing. Even when fetal growth and gestation length have been normal, the maturing fetus can still be adversely impacted by both physical events and psychological challenges to the mother during the prenatal period. The following research evaluated 413 rhesus monkeys from 7 different types of pregnancies to determine which conditions significantly influenced the behavioral responsiveness and state of the young infant. A standardized test battery modeled after the Neonatal Behavioral Assessment Scale for human newborns was employed. The largest impairments in orientation and increases in infant emotional reactivity were seen when female monkeys drank alcohol, even though consumed at only moderate levels during part of the pregnancy. The infants' ability to focus and attend to visual and auditory cues was also affected when the gravid female's adrenal hormones were transiently elevated for 2 weeks by ACTH administration. In addition, responses to tactile and vestibular stimulation were altered by both this ACTH treatment and psychological disturbance during gestation. Conversely, a 2-day course of antenatal corticosteroids 1 month before term resulted in infants with lower motor activity and reactivity. These findings highlight several pregnancy conditions that can affect a young infant's neurobehavioral status, even when otherwise healthy, and demonstrate that alterations or deficits are specific to the type of insult experienced by the mother and fetus.
    Full-text · Article · Nov 2010 · Developmental Psychobiology
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    [Show abstract] [Hide abstract] ABSTRACT: (18)F-Fallypride and (11)C-FLB457 are commonly used PET radioligands for imaging extrastriatal dopamine D(2)/D(3) receptors, but differences in their in vivo kinetics may affect the sensitivity for measuring subtle changes in receptor binding. Focusing on regions of low binding, a direct comparison of the kinetics of (18)F-fallypride and (11)C-FLB457 was made using a MI protocol. Injection protocols were designed to estimate K(1), k(2), f(ND)k(on), B(max), and k(off) in the midbrain and cortical regions of the rhesus monkey. (11)C-FLB457 cleared from the arterial plasma faster and yielded a ND space distribution volume (K(1)/k(2)) that is three times higher than (18)F-fallypride, primarily due to a slower k(2) (FAL:FLB; k(2)=0.54 min(-1):0.18 min(-1)). The dissociation rate constant, k(off), was slower for (11)C-FLB457, resulting in a lower K(Dapp) than (18)F-fallypride (FAL:FLB; 0.39 nM:0.13 nM). Specific D(2)/D(3) binding could be detected in the cerebellum for (11)C-FLB457 but not (18)F-fallypride. Both radioligands can be used to image extrastriatal D(2)/D(3) receptors, with (11)C-FLB457 providing greater sensitivity to subtle changes in low-receptor-density cortical regions and (18)F-fallypride being more sensitive to endogenous dopamine displacement in medium-to-high-receptor-density regions. In the presence of specific D(2)/D(3) binding in the cerebellum, reference region analysis methods will give a greater bias in BP(ND) with (11)C-FLB457 than with (18)F-fallypride.
    Full-text · Article · May 2010 · Journal of cerebral blood flow and metabolism: official journal of the International Society of Cerebral Blood Flow and Metabolism
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    [Show abstract] [Hide abstract] ABSTRACT: Sensory processing disorder, characterized by over- or under-responsivity to non-noxious environmental stimuli, is a common but poorly understood disorder. We examined the role of prenatal alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and striatal dopamine (DA) function on behavioral measures of sensory responsivity to repeated non-noxious sensory stimuli in macaque monkeys. Results indicated that early gestation alcohol exposure induced behavioral under-responsivity to environmental stimuli in monkeys carrying the short (s) rh5-HTTLPR allele compared to both early-exposed monkeys homozygous for the long (l) allele and monkeys from middle-to-late exposed pregnancies and controls, regardless of genotype. Moreover, prenatal timing of alcohol exposure altered the relationship between sensory scores and DA D(2)R availability. In early-exposed monkeys, a positive relationship was shown between sensory scores and DA D(2)R availability, with low or blunted DA function associated with under-responsive sensory function. The opposite pattern was found for the middle-to-late gestation alcohol-exposed group. These findings raise questions about how the timing of prenatal perturbation and genotype contributes to effects on neural processing and possibly alters neural connections.
    Full-text · Article · Nov 2009 · Frontiers in Integrative Neuroscience
  • Mary L. Schneider · Stephen J. Suomi
    [Show abstract] [Hide abstract] ABSTRACT: The relationship between temperamental expressions of emotionality and postrotary nystagmus responses was investigated in infant rhesus monkeys. Thirty-three infants were tested on nine occasions during the first months of life using instruments adapted from human developmental tests. Assessments included a laboratory assessment of temperament and an adaptation of the Southern California Postrotary Nystagmus Test. Correlations among the nine postrotary nystagmus sessions were consistently high and positive indicating high test-retest stability of the postrotary nystagmus test for rhesus monkey infants. Infants with high rating on early laboratory assessments of fearfulness were found to exhibit shortened durations of postrotary nytagmus, shortened excursion lengths of postrotary nystagmus, more variance or day-to-day fluctuation in postrotary nystgmus, and less stability of rank order across the nine testing sessions when compared to infants categorized as bold. Possible mechanisms underlying the suggested ling between temperament and postrotary nystagmus responses in monkeys, as well as directions for future research, are discussed.
    No preview · Article · Jul 2009 · Physical & Occupational Therapy in Pediatrics