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Accepted (AM)Open Access (License Unspecified), Open
Journal article
Epigenetic and pharmacological regulation of 5HT3 receptors controls compulsive ethanol seeking in mice
The European journal of neuroscience, v 39(6), pp 999-1008
01 Mar 2014
PMID: 24772465
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Factors underlying individual vulnerability to develop alcoholism are largely unknown. In humans, the risk for alcoholism is associated with elevated cue reactivity. Recent evidence suggests that in animal models, reactivity to reward-paired cues is predictive of addictive behaviors. To model cue reactivity in mice, we used a Pavlovian approach (PA) paradigm in which mice were trained to associate a cue with delivery of a food reinforcer. We then investigated the relationship between PA status with habitual and compulsive-like ethanol seeking. After training mice to respond for 10% ethanol, habitual behavior was investigated using both an outcome devaluation paradigm, in which ethanol was devalued via association with lithium chloride-induced malaise, and a contingency degradation paradigm in which the relationship between action and outcome was disrupted. Compulsive-like behavior was investigated in a modified conditioned place preference paradigm in which footshock was paired with the reward-paired chamber. PA was found to be predictive of habitual and compulsive-like ethanol seeking. Additionally, innate risk status was related to epigenetic changes in the gene encoding the requisite subunit of the 5HT3 receptor, Htr3a, as well as 5HT3A protein expression in the amygdala. We then used pharmacological tools to demonstrate that risk status determines the ability of a 5HT3 antagonist to reduce compulsive ethanol seeking. These data indicate that risk status can be identified prior to any alcohol exposure by assessment of cue reactivity, and further that this endophenotype may be predictive of response to pharmacological treatment for components of alcoholism.
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Details
- Title
- Epigenetic and pharmacological regulation of 5HT3 receptors controls compulsive ethanol seeking in mice
- Creators
- Jacqueline M. Barker - Yale UniversityHuiping Zhang - Yale UniversityJ. Joshua Villafane - Yale UniversityTiffany L. Wang - Yale UniversityMary M. Torregrossa - Yale UniversityJane R. Taylor - Yale University
- Publication Details
- The European journal of neuroscience, v 39(6), pp 999-1008
- Publisher
- Wiley
- Number of pages
- 10
- Grant note
- R03AA017776 / NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Alcohol Abuse & Alcoholism (NIAAA) AA012870; AA017776; AA020135; DA031745; DA022891 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Connecticut Department of Mental Health and Addiction Services R00DA022891 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Web of Science ID
- WOS:000332758500011
- Scopus ID
- 2-s2.0-84896132267
- Other Identifier
- 991020100076104721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Neurosciences