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Neonatal sensory processing (tactile and vestibular function) was tested in 78 rhesus macaques from two experiments. At ages 4-5 years, striatal dopamine D 2 receptor binding was examined using positron emission tomography. At ages 5-7 years, adult sensory processing was assessed. Findings were: (a) prenatal stress exposure yielded less optimal neonatal sensory processing; (b) animals carrying the short rh5-HTTLPR allele had less optimal neonatal sensory scores than monkeys homozygous for the long allele; (c) neonatal sensory processing was significantly related to striatal D 2 receptor binding for carriers of the short allele, but not for animals homozygous for the long allele; and (d) there was moderate developmental continuity in sensory processing from the neonatal period to adulthood., (© 2016 The Authors. Child Development © 2016 Society for Research in Child Development, Inc.)

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., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

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: [(18)F]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., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: 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., Methods: 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., Results: 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., Conclusion: 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., (Copyright © 2011 by the Research Society on Alcoholism.)

Background: Moderate prenatal alcohol exposure can cause impairments even in the absence of gross morphological defects associated with fetal alcohol syndrome. The basal ganglia, which include the dopamine-rich striatum, are sensitive to fetal alcohol-induced injury. In this study, we manipulated the timing of moderate-level alcohol exposure and compared the risk of adverse effects on striatal dopamine (DA) system function in rhesus monkeys., Methods: Thirty-five young adult rhesus monkeys (Macaca mulatta) from four groups of females were assessed: (1) an early alcohol-exposed group (n=9), in which mothers voluntarily consumed 0.6 g/kg alcohol solution on gestational days 0 through 50; (2) a middle-to-late gestation alcohol-exposed group (n=7), in which mothers voluntarily consumed 0.6 g/kg alcohol solution on gestational days 50 through 135; (3) a continuous-exposure group (n=9), in which mothers voluntarily consumed 0.6 g/kg alcohol solution on days 0 through 135; and (4) controls (n=10), in which mothers voluntarily consumed an isocaloric control solution on gestational days 0 through 50, 50 through 135, or 0 through 135. We studied striatal DA system function by positron emission tomography in separate scans for trapping of [(18)F]fallypride and 6-[(18)F]fluoro-m-tyrosine to assess striatal DA D2 receptor (D2R) binding and DA synthesis, respectively, via dopadecarboxylase activity., Results: Moderate-level alcohol exposure during early gestation and continuous exposure throughout gestation (early + middle-to-late exposure) reduced the striatal D2R binding to DA synthesis ratio, whereas middle-to-late alcohol gestation exposure increased the striatal D2R binding to DA synthesis ratio. The continuous-exposure group showed the largest effect. Moreover, the D2R binding/DA synthesis ratio was related to neonatal neurobehavior measures in control monkeys, but these relationships were disrupted in the fetal alcohol-exposed monkeys., Conclusion: These results suggest that the vulnerability of the DA system to the effects of moderate doses of alcohol during gestation depend on the timing of the alcohol exposure. Early-gestation moderate alcohol exposure resulted in a reduction or blunting of dopaminergic function in adulthood, whereas middle to late exposure (without early exposure) either induced the opposite pattern or heightened dopaminergic function. Continuously exposed monkeys showed the largest effect, suggesting that the sooner women stop drinking, the better it is for the fetus.

Background We examined the effects of moderate prenatal alcohol exposure and/or prenatal stress exposure on (D1R) binding in a non human primate model. The dopamine D1R 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 D1R. We expected that prenatal insults would lead to alterations in D1R binding in prefrontal cortex (PFC) and striatum in adulthood. Methods 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 [11C]SCH 23390. Radiotracer binding in PFC and striatum was evaluated by 2 (alcohol) × 2 (stress) × 2 (sex) analysis of variance. Results In PFC, a significant alcohol × sex interaction was observed with prenatal alcohol exposure leading to increased [11C]SCH 23390 binding in male monkeys. No main effect of prenatal alcohol or prenatal stress exposure was observed. Conclusions These results suggest that prenatal alcohol exposure results in long-term increases in prefrontal dopamine D1R binding in males. This may help explain gender differences in the prevalence of neurodevelopmental disorders consequent to prenatal alcohol exposure. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]