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Neurochemical Heterogeneity of Rats Predicted by Different Measures to be High Ethanol Consumers
Journal article   Open access   Peer reviewed

Neurochemical Heterogeneity of Rats Predicted by Different Measures to be High Ethanol Consumers

Jessica R. Barson, Shawn E. Fagan, Guo-Qing Chang and Sarah F. Leibowitz
Alcoholism, clinical and experimental research, v 37(s1), pp E141-E151
01 Jan 2013
DOI: https://doi.org/10.1111/j.1530-0277.2012.01858.x
PMID: 22725682
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://europepmc.org/articles/pmc3984010View
Accepted (AM)Open Access (License Unspecified),  Open
url
https://doi.org/10.1111/j.1530-0277.2012.01858.xView
Published, Version of Record (VoR) Open

Abstract

Life Sciences & Biomedicine Science & Technology Substance Abuse
Background Alcoholism is a heterogeneous disease, with subjects possibly differing both in the best measure that predicts their excess consumption and in their most effective pharmacotherapy. Two different measures, high novelty-induced activity and high-fat-induced triglycerides (TGs), are known to identify subgroups of animals prone to consuming higher amounts of ethanol (EtOH). The question investigated here is whether these subgroups are, in fact, similar in their neurochemical phenotype that may contribute to their overconsumption. Methods EtOH-naive, SpragueDawley rats were subgrouped based on the 2 predictor measures of activity or TG levels, and then quantitative real-time polymerase chain reaction and digoxigenin-labeled in situ hybridization were used to measure their expression of hypothalamic peptides that affect EtOH intake. In additional subgroups subsequently trained to drink 9% EtOH, the opioid antagonist and alcoholism medication, naltrexone, was tested at a low dose (0.02 mg/kg, s.c.) to determine the rats' sensitivity to its effects. Results The 2 measures, while both effective in predicting amount of EtOH intake, were found to identify distinctive subgroups. Rats with high compared to low activity exhibited significantly greater expression of galanin and enkephalin in the paraventricular nucleus (PVN) and of orexin in the perifornical lateral hypothalamus (PFLH), but no difference in melanin-concentrating hormone in PFLH or neuropeptide Y in arcuate nucleus. This contrasts with rats having high TG, which exhibited greater expression only of PVN galanin, along with reduced PFLH orexin. The high-activity rats with elevated enkephalin, but not high-TG rats, were also unusually sensitive to naltrexone, which significantly reduced their alcohol intake. Conclusions In addition to revealing differences in endogenous peptides and drug responsiveness in predicted high EtOH drinkers, this study demonstrates that these disturbances differ markedly between the 2 at-risk subgroups. This indicates that simple tests may be effective in identifying subjects most responsive to a specific pharmacotherapy.

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Web of Science research areas
Substance Abuse
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