title: Effects of early life stress on drinking and serotonin system activity in rhesus macaques: 5-hydroxyindoleacetic acid in cerebrospinal fluid predicts brain tissue levels.
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.
authors.affiliation: Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, NC 27157, USA.
authors.forename: Kimberly N
authors.initials: KN
authors.lastname: Huggins
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Mathews
authors.forename: Jason L
authors.initials: JL
authors.lastname: Locke
authors.forename: Kendall T
authors.initials: KT
authors.lastname: Szeliga
authors.forename: David P
authors.initials: DP
authors.lastname: Friedman
authors.forename: Allyson J
authors.initials: AJ
authors.lastname: Bennett
authors.forename: Sara R
authors.initials: SR
authors.lastname: Jones
mesh_terms: D000428:Alcohol Drinking / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002845:Chromatography; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid* / Q000378:metabolism; D008253:Macaca mulatta; D008297:Male; D008426:Maternal Deprivation; D012701:Serotonin / Q000378:metabolism*
chemical_list: D012701:Serotonin; D000431:Ethanol; D006897:Hydroxyindoleacetic Acid