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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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Previous studies have suggested a modulatory role of the 5-HT2 receptor system in the behavioral effects of ethanol. The present study examined the discriminative stimulus effects of the 5-HT2A/2C agonist (-)-dimethoxy-4-indophenly-2-aminopropane (DOI) and the 5-HT2A antagonist ketanserin in rats trained to discriminate either 1.5 g/kg of ethanol from water (intragastrically, n= 7) or 2.0 g/kg of ethanol from water (intragastrically, n= 8). In substitution tests, neither DOI (0.3 to 1.0 mg/kg, ip) nor ketanserin (3.0 to 17.0 mg/kg, ip) produced discriminative stimulus effects similar to either training dose of ethanol, although decreases in rates of responding were significant at the highest doses tested. Likewise, when given in combination with ethanol, neither 5-HT2 ligand shifted the ethanol-dose response determination in either the 1.5 or 2.0 g/kg ethanol training groups. DOI in combination with ethanol did not alter rates of responding, whereas ketanserin in combination with ethanol significantly decreased response rates. Thus, the 5-HT2A receptor ligands do not appreciably affect the discriminative stimulus effects of ethanol, in contrast to previous results with 5-HT1B ligands. [ABSTRACT FROM AUTHOR]