Development of Ethanol Withdrawal-Related Sensitization and Relapse Drinking in Mice Selected for High- or Low-Ethanol Preference: WITHDRAWAL SENSITIZATION AND RELAPSE DRINKING IN HAP AND LAP MICE
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BACKGROUND: Previous studies have shown that high alcohol consumption is associated with low withdrawal susceptibility, while at the same time, other studies have shown that exposure to ethanol vapor increases alcohol drinking in rats and mice. In the present studies, we sought to shed light on this seeming contradiction using mice selectively bred for High- (HAP) and Low- (LAP) Alcohol Preference, first, assessing these lines for differences in signs of ethanol withdrawal and second, for differences in the efficacy of intermittent alcohol vapor exposure on elevating subsequent ethanol intake. METHODS: Experiment 1 examined whether these lines of mice differed in ethanol withdrawal-induced CNS hyperexcitability and the development of sensitization to this effect following intermittent ethanol vapor exposure. Adult HAP and LAP lines (replicates 1 and 2), and the C3H/HeNcr inbred strain (included as a control genotype for comparison purposes) received intermittent exposure to ethanol vapor and were evaluated for ethanol withdrawal-induced seizures assessed by scoring handling-induced convulsions (HIC). Experiment 2 examined the influence of chronic intermittent ethanol exposure on voluntary ethanol drinking. Adult male and female HAP-2 and LAP-2 mice, along with male C57BL/6J (included as comparative controls) were trained to drink 10% ethanol using a limited access (2 h/d) 2-bottle choice paradigm. After stable baseline daily intake was established, mice received chronic intermittent ethanol vapor exposure in inhalation chambers. Ethanol intake sessions resumed 72 hours after final ethanol (or air) exposure for 5 consecutive days. RESULTS: Following chronic ethanol treatment, LAP mice exhibited overall greater withdrawal seizure activity compared with HAP mice. In Experiment 2, chronic ethanol exposure/withdrawal resulted in a significant increase in ethanol intake in male C57BL/6J, and modestly elevated intake in HAP-2 male mice. Ethanol intake for male control mice did not change from baseline levels of intake. In contrast, HAP-2 female and LAP-2 mice of both sexes did not show changes in ethanol intake as a consequence of intermittent ethanol exposure. CONCLUSIONS: Overall, these results indicate that the magnitude of ethanol withdrawal-related seizures is inversely related to inherited ethanol intake preference. Additionally, intermittent ethanol vapor exposure appears more likely to affect high-drinking mice (C57BL/6J and HAP-2) than low drinkers, although these animals are less affected by ethanol withdrawal.
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Chronic alcohol exposure and withdrawal result in modest elevations of alcohol intake in male High Alcohol Preferring 2 mice, but not in female High Alcohol Preferring 2 mice.
“Chronic alcohol exposure and withdrawal result in modest elevations of alcohol intake in male High Alcohol Preferring 2 mice.In contrast, female High Alcohol Preferring 2 mice did not show changes in alcohol intake (Lopez et al., 2011).”
From Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development (2021) · cites this paper as Lopez et al., 2011
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- Authors
- Lopez, M. F., Grahame, N. J., & Becker, H. C.
- Affiliations
- Medical University of South Carolina (US)
- Corresponding author
- Lopez, Marcelo F.
- Venue
- Alcoholism: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2011-02-11
- Volume
- 35
- Issue
- 5
- Pages
- 953-962
- ISSN
- 0145-6008 (ISSN-L)
- PMC
- PMC3083457
- OpenAlex
- W1767963567
- Cited by
- 41
- References
- 46
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 2 · 2021: 4 · 2020: 4 · 2019: 1 · 2018: 2 · 2016: 4 · 2015: 3 · 2014: 6 · 2013: 3 · 2012: 7
- FWCI
- 2.38
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R24AA015512, AA 10761, U24AA015512, U01AA013483, AA13483, AA 015512, AA014095, U01AA014095, P50AA010761)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- ethanol withdrawal, alcohol preference, ethanol vapor exposure, voluntary ethanol consumption, genetic selection, sex differences, C57BL/6J mice
- MeSH terms
- Alcohol Drinking, Ethanol, Alcoholism, Animals, Female, Male, Mice, Inbred C3H, Mice, Inbred C57BL, Recurrence, Species Specificity, Substance Withdrawal Syndrome, Alcohol Withdrawal Seizures, Mice
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