| Title: | Moderate prenatal alcohol exposure and serotonin genotype interact to alter CNS serotonin function in rhesus monkey offspring |
| Author(s): | Schneider ML; Moore CF; Barr CS; Larson JA; Kraemer GW; |
| Address: | "Department of Kinesiology, University of Wisconsin-Madison, 53706, USA. schneider@education.wisc.edu" |
| DOI: | 10.1111/j.1530-0277.2010.01421.x |
| ISSN/ISBN: | 1530-0277 (Electronic) 0145-6008 (Print) 0145-6008 (Linking) |
| 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" |
| Keywords: | Animals Central Nervous System/drug effects/*physiology Ethanol/*administration & dosage Female Genotype Hydroxyindoleacetic Acid/cerebrospinal fluid Macaca mulatta Male Pregnancy Prenatal Exposure Delayed Effects/cerebrospinal fluid/*genetics Random Allo; |
| Notes: | "MedlineSchneider, Mary L Moore, Colleen F Barr, Christina S Larson, Julie A Kraemer, Gary W eng R01 AA010079-14/AA/NIAAA NIH HHS/ AA12277/AA/NIAAA NIH HHS/ AA10079/AA/NIAAA NIH HHS/ R01 AA012277-10/AA/NIAAA NIH HHS/ R01 AA012277/AA/NIAAA NIH HHS/ R01 AA010079/AA/NIAAA NIH HHS/ Comparative Study Research Support, N.I.H., Extramural England 2011/02/08 Alcohol Clin Exp Res. 2011 May; 35(5):912-20. doi: 10.1111/j.1530-0277.2010.01421.x. Epub 2011 Feb 5" |
