Moderate Prenatal Alcohol Exposure and Serotonin Genotype Interact to Alter CNS Serotonin Function in Rhesus Monkey Offspring

Authors

  • Mary L. Schneider,

    1. From the Department of Kinesiology (MLS, JAL), University of Wisconsin-Madison, Madison, Wisconsin; Department of Psychology (CFM), University of Wisconsin-Madison, Madison, Wisconsin; Harlow Center for Biological Psychology (MLS, JAL), University of Wisconsin-Madison, Madison, Wisconsin; National Institute on Alcohol Abuse and Alcoholism (NIAAA) (CSB), National Institute of Health, Maryland; and Department of Psychology (GWK), University of Toronto, Toronto, Ontario, Canada.
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  • Colleen F. Moore,

    1. From the Department of Kinesiology (MLS, JAL), University of Wisconsin-Madison, Madison, Wisconsin; Department of Psychology (CFM), University of Wisconsin-Madison, Madison, Wisconsin; Harlow Center for Biological Psychology (MLS, JAL), University of Wisconsin-Madison, Madison, Wisconsin; National Institute on Alcohol Abuse and Alcoholism (NIAAA) (CSB), National Institute of Health, Maryland; and Department of Psychology (GWK), University of Toronto, Toronto, Ontario, Canada.
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  • Christina S. Barr,

    1. From the Department of Kinesiology (MLS, JAL), University of Wisconsin-Madison, Madison, Wisconsin; Department of Psychology (CFM), University of Wisconsin-Madison, Madison, Wisconsin; Harlow Center for Biological Psychology (MLS, JAL), University of Wisconsin-Madison, Madison, Wisconsin; National Institute on Alcohol Abuse and Alcoholism (NIAAA) (CSB), National Institute of Health, Maryland; and Department of Psychology (GWK), University of Toronto, Toronto, Ontario, Canada.
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  • Julie A. Larson,

    1. From the Department of Kinesiology (MLS, JAL), University of Wisconsin-Madison, Madison, Wisconsin; Department of Psychology (CFM), University of Wisconsin-Madison, Madison, Wisconsin; Harlow Center for Biological Psychology (MLS, JAL), University of Wisconsin-Madison, Madison, Wisconsin; National Institute on Alcohol Abuse and Alcoholism (NIAAA) (CSB), National Institute of Health, Maryland; and Department of Psychology (GWK), University of Toronto, Toronto, Ontario, Canada.
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  • Gary W. Kraemer

    1. From the Department of Kinesiology (MLS, JAL), University of Wisconsin-Madison, Madison, Wisconsin; Department of Psychology (CFM), University of Wisconsin-Madison, Madison, Wisconsin; Harlow Center for Biological Psychology (MLS, JAL), University of Wisconsin-Madison, Madison, Wisconsin; National Institute on Alcohol Abuse and Alcoholism (NIAAA) (CSB), National Institute of Health, Maryland; and Department of Psychology (GWK), University of Toronto, Toronto, Ontario, Canada.
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Reprint requests: Mary L. Schneider, PhD, Department of Kinesiology, Occupational Therapy Program, University of Wisconsin-Madison, 2175 Medical Science Center, 1400 University Ave. Madison, WI 53706; Tel.: +1 608- 265-5118; Fax: +1 608- 262-6020; E-mail: schneider@education.wisc.edu

Abstract

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.

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