4 years ago

Low Inherent Sensitivity to the Intoxicating Effects of Ethanol in Rhesus Monkeys with Low CSF Concentrations of the Serotonin Metabolite 5-Hydroxyindoleacetic Acid

Christina S. Barr, Ryno Kruger, Melanie Schwandt, J. Dee Higley, Bradley M. Cooke, Stephen J. Suomi, David Goldman, Angus Bennion, Elizabeth K. Wood, Stephen Lindell
Introduction Type 2 Alcoholism is characterized by low serotonin system functioning and has a high degree of heritability, with offspring of alcoholics often showing a reduced response to the intoxicating effects of ethanol, which is thought to be marker for future alcohol use disorders (AUDs). As such, an important aim of studies investigating the origins of AUDs is understanding the relationship between serotonin system functioning and level of intoxication. A nonhuman primate model was used to evaluate observational ratings of sensitivity to ethanol and to further investigate the relationship between central serotonin activity and behavioral response to ethanol. Materials and Methods Cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA) were obtained from four cohorts of alcohol-naïve, adolescent rhesus macaques (N=82, 45 females, 37 males). One to three months after the CSF sample, subjects were administered a standardized intravenous (IV) ethanol bolus (males: 2.1 g/kg body weight, females: 2.0 g/kg body weight), placed into an open top, clear Plexiglas™ chamber suspended from the ceiling, and their latency to escape was recorded as a measure of the degree of intoxication. Thereafter, subjects were rated using a Likert scale for the degree of intoxication during a 30-minute observation period. Results Our results indicate that latency to escape from the chamber was associated with intoxication ratings (p = 0.0001) following the standardized IV administration of ethanol. Low CSF 5-HIAA concentrations predicted short escape latency (p = 0.006) and were associated with low intoxication ratings (p = 0.02), indicating that low CNS serotonin functioning is related to relative insensitivity to the intoxicating effects of alcohol. Discussion Our study shows that, in monkeys exposed to alcohol for the first time, objective measures of intoxication are associated with subjective ratings for intoxication and both were associated with CSF 5-HIAA concentrations. Our data confirm and extend the finding that low CNS serotonin functioning is predictive of intrinsic low sensitivity to the intoxicating effects of ethanol. This article is protected by copyright. All rights reserved.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1111/acer.13552

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