Effects of early life stress on drinking and serotonin system activity in rhesus macaques: 5-hydroxyindoleacetic acid in cerebrospinal fluid predicts brain tissue levels

• Published in: Alcohol (Fayetteville, N.Y.) N.Y.), 2012-06, Vol.46 (4), p.371-376
• Main Authors: Huggins, Kimberly N, Mathews, Tiffany A, Locke, Jason L, Szeliga, Kendall T, Friedman, David P, Bennett, Allyson J, Jones, Sara R
• Format: Article
• Language: English
• Subjects: Alcohol Drinking - cerebrospinal fluid; Alcohol Drinking - metabolism; Alcohol use; Alcoholism; Analysis of Variance; Animals; Behavior; Brain; Brain - metabolism; Caudate; Chromatography; Disease Models, Animal; Ethanol; Ethanol - pharmacology; Fluids; Hippocampus; Hydroxyindoleacetic Acid - cerebrospinal fluid; Hydroxyindoleacetic Acid - metabolism; Macaca mulatta; Male; Maternal Deprivation; Metabolite; Metabolites; Monkeys & apes; Primates; Psychiatry; Putamen; Serotonin; Serotonin - metabolism; Stress; Studies; Substantia nigra; Tissue content
• ISSN: 0741-8329; 1873-6823
• DOI: 10.1016/j.alcohol.2011.11.003

Abstract Early childhood stress is a risk factor for the development of substance-abuse disorders. A nonhuman primate model of early life stress, social impoverishment through nursery-rearing rather than mother-rearing, has been shown to produce increased impulsive and anxiety-like behaviors, cognitive and motor deficits, and increased alcohol consumption. These behavioral changes have been linked to changes in cerebrospinal fluid (CSF) levels of 5-hydroxyindoleacetic acid (5-HIAA), a serotonin (5-HT) metabolite. The effects of different rearing conditions on ethanol drinking and three measures of 5-HT function in the central nervous system were evaluated, including CSF 5-HIAA levels and tissue levels of 5-HT and 5-HIAA in brain samples. Brain samples were taken from the dorsal caudate, putamen, substantia nigra (SN) pars reticulata, SN pars compacta and hippocampus. There was a clear effect of rearing condition on the 5-HT system. Overall 5-HIAA and 5-HIAA/5-HT ratio measures of 5-HT turnover were significantly lower in nursery reared compared to mother-reared animals. In addition, there was a strong within-subject correlation between CSF and brain tissue 5-HIAA levels. Ethanol drinking was greater in nursery reared monkeys, consistent with previous results. These findings show that CSF 5-HIAA measurements can be used to predict brain 5-HT activity that may be involved in behavioral outcomes such as anxiety and alcohol consumption. Thus, CSF sampling may provide a minimally invasive test for neurochemical risk factors related to alcohol abuse.