Selectively bred crossed high-alcohol-preferring mice drink to intoxication and develop functional tolerance, but not locomotor sensitization during free-choice ethanol access
Open accessAbstract
BACKGROUND: Crossed high-alcohol-preferring (cHAP) mice were selectively bred from a cross of the HAP1 × HAP2 replicate lines and demonstrate blood ethanol concentrations (BECs) during free-choice drinking reminiscent of those observed in alcohol-dependent humans. In this report, we investigated the relationship between free-choice drinking, intoxication, tolerance, and sensitization in cHAP mice. We hypothesized that initially mice would become ataxic after drinking alcohol, but that increased drinking over days would be accompanied by increasing tolerance to the ataxic effects of ethanol (EtOH). METHODS: Male and female cHAP mice had free-choice access to 10% EtOH and water (E), while Water mice (W) had access to water alone. In experiment 1, the first drinking experience was monitored during the dark portion of the cycle. Once E mice reached an average intake rate of ≥1.5 g/kg/h, they, along with W mice, were tested for footslips on a balance beam, and BECs were assessed. In experiments 2, 3, and 4, after varying durations of free-choice 10% EtOH access (0, 3, 14, or 21 days), mice were challenged with 20% EtOH and tested for number of footslips on a balance beam or locomotor stimulant response. Blood was sampled for BEC determination. RESULTS: We found that cHAP mice rapidly acquire alcohol intakes that lead to ataxia. Over time, cHAP mice developed behavioral tolerance to the ataxic effects of alcohol, paralleled by escalating alcohol consumption. However, locomotor sensitization did not develop following 14 days of free-choice EtOH access. CONCLUSIONS: Overall, we observed increases in free-choice drinking with extended alcohol access paralleled by increases in functional tolerance, but not locomotor sensitization. These data support our hypothesis that escalating free-choice drinking over days in cHAP mice is driven by tolerance to alcohol's behavioral effects. These data are the first to demonstrate that escalating free-choice consumption is accompanied by increasing alcohol tolerance. In addition to buttressing the hypothesized importance of tolerance in drinking, our findings suggest that cHAP mice may be a unique, translational resource for studying tolerance as a contributor to and consequence of chronic, excessive EtOH consumption.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Tolerance theory implies that attenuation of subjective alcohol responses over time plays a key role in the development of addiction.
“Tolerance, a diagnostic criteria for AUD from DSM-III (1980) to DSM-5 (2013)(8), implies that attenuation of subjective alcohol responses over time plays a key role in the development of addiction.”
From A Prospective 5-Year Re-examination of Alcohol Response in Heavy Drinkers Progressing in Alcohol Use Disorder (2016) · cites this paper as [5]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Diagnostic and Statistical Manual of Mental Disorders.
Widiger, T. A. (2000) · Oxford University Press eBooks · doi:10.1037/10518-009 · Cited by 19,767 · see citing works
The psychology and neurobiology of addiction: an incentive–sensitization view
Robinson, T. E., & Berridge, K. C. (2000) · Addiction · doi:10.1046/j.1360-0443.95.8s2.19.x · Cited by 1,507 · see citing works
Rewarding, stimulant, and sedative alcohol responses and relationship to future binge drinking
King, A. C., de Wit, H., McNamara, P. J., & Cao, D. (2011) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2011.26 · Cited by 379 · see citing works
Mouse inbred strain differences in ethanol drinking to intoxication
Rhodes, J. S., Ford, M. M., Yu, C. ‐., Brown, L. L., Finn, D. A., Garland, T., & Crabbe, J. C. (2006) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2006.00210.x · Cited by 340 · see citing works
Localization of Genes Affecting Alcohol Drinking in Mice
Phillips, T. J., Crabbe, J. C., Metten, P., & Belknap, J. K. (1994) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1994.tb00062.x · Cited by 291 · see citing works
A role for sensitization in craving and relapse in cocaine addiction
Kalivas, P. W., Pierce, R. C., Cornish, J. L., & Sorg, B. A. (1998) · Journal of Psychopharmacology · doi:10.1177/026988119801200107 · Cited by 253 · see citing works
Homeostatic theory of drug tolerance: a general model of physiological adaptation
Poulos, C. X., & Cappell, H. (1991) · Psychological Review · doi:10.1037/0033-295x.98.3.390 · Cited by 221 · see citing works
Phillips, T. J., Huson, M., Gwiazdon, C., Burkhart‐Kasch, S., & Shen, E. H. (1995) · Alcoholism: Clinical and Experimental Research · doi:10.1111/j.1530-0277.1995.tb01502.x · Cited by 205 · see citing works
Different sensitivities to ethanol in alcohol-preferring and -nonpreferring rats
Lumeng, L., Waller, M. B., McBride, W. J., & Li, T. (1982) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(82)90023-5 · Cited by 166 · see citing works
Chronic tolerance and sensitization to alcohol in sons of alcoholics
Newlin, D. B., & Thomson, J. B. (1991) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1991.tb00537.x · Cited by 165 · see citing works
Mello, N. K., & Mendelson, J. H. (1970) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)28543-3 · Cited by 135 · see citing works
Leeman, R. F., Heilig, M. A., Cunningham, C. L., Stephens, D., Duka, T., & O’Malley, S. S. (2010) · Addiction Biology · doi:10.1111/j.1369-1600.2009.00192.x · Cited by 130 · see citing works
The Complexity of Alcohol Drinking: Studies in Rodent Genetic Models
Crabbe, J. C., Phillips, T. J., & Belknap, J. K. (2010) · Behavior Genetics · doi:10.1007/s10519-010-9371-z · Cited by 115 · see citing works
Lessov, C. N., Palmer, A. A., Quick, E., & Phillips, T. J. (2001) · Psychopharmacology · doi:10.1007/s002130100699 · Cited by 102 · see citing works
Duration of sensitization to the locomotor stimulant effects of ethanol in mice
Lessov, C. N., & Phillips, T. J. (1998) · Psychopharmacology · doi:10.1007/s002130050525 · Cited by 92 · see citing works
Genetic differences in tolerance and sensitization to the sedative/hypnotic effects of alcohol
Kurtz, D. L., Stewart, R. B., Zweifel, M., Li, T., & Froehlich, J. C. (1996) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(95)02055-1 · Cited by 89 · see citing works
Genotypic differences in ethanol sensitivity in two tests of motor incoordination
Crabbe, J. C., Metten, P., Yu, C.-H., Schlumbohm, J. P., Cameron, A. J., & Wahłsten, D. (2003) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00132.2003 · Cited by 81 · see citing works
Newlin, D. B., & Thomson, J. B. (1999) · Experimental and Clinical Psychopharmacology · doi:10.1037//1064-1297.7.3.234 · Cited by 78 · see citing works
Newlin, D. B., & Thomson, J. B. (1999) · Experimental and Clinical Psychopharmacology · doi:10.1037/1064-1297.7.3.234 · Cited by 78 · see citing works
Grahame, N. J., Rodd‐Henricks, K., Li, T., & Lumeng, L. (2000) · Psychopharmacology · doi:10.1007/s002130000388 · Cited by 77 · see citing works
Self-citationOberlin, B. G., Best, C., Matson, L. M., Henderson, A. N., & Grahame, N. J. (2010) · Behavior Genetics · doi:10.1007/s10519-010-9394-5 · Cited by 72 · see citing works
Self-citationLumeng, L., & Li, T. (1986) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(86)90079-1 · Cited by 72 · see citing works
GABAergic modulation of binge-like ethanol intake in C57BL/6J mice
Moore, E. M., Serio, K. M., Goldfarb, K. J., STEPANOVSKA, S., Linsenbardt, D. N., & Boehm, S. L. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2007.07.011 · Cited by 69 · see citing works
Self-citationMatson, L. M., & Grahame, N. J. (2011) · Addiction Biology · doi:10.1111/j.1369-1600.2011.00412.x · Cited by 68 · see citing works
Self-citationTolerance and the etiology of alcoholism: Hypothesis and mechanism
Tabakoff, B., & Hoffman, P. L. (1988) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1988.tb00157.x · Cited by 59 · see citing works
Linsenbardt, D. N., Moore, E. M., Griffin, K. D., Gigante, E. D., & Boehm, S. L. (2011) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2011.01459.x · Cited by 46 · see citing works
Self-citationMatson, L. M., Liangpunsakul, S., Crabb, D. W., et al. (2012) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2012.01873.x · Cited by 38 · see citing works
Self-citationDidone, V., Quoilin, C., Tirelli, E., & Quertemont, É. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1266-9 · Cited by 36 · see citing works
Does context influence the duration of locomotor sensitization to ethanol in female DBA/2J mice?
Boehm, S. L., Goldfarb, K. J., Serio, K. M., et al. (2007) · Psychopharmacology · doi:10.1007/s00213-007-1022-6 · Cited by 33 · see citing works
Self-citationDarbra, S., Prat, G., Pallarés, M., & Ferré, N. (2002) · Journal of Psychopharmacology · doi:10.1177/026988110201600107 · Cited by 21 · see citing works
Fritz, B. M., Grahame, N. J., & Boehm, S. L. (2012) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2012.00830.x · Cited by 18 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Cicero T 1980 Alcohol self-administration, tolerance, and withdrawal in humans and animals: theoretical and methodological issues, in Alcohol tolerance and dependence Alcohol tolerance and dependence RIGTER HC J Elsevier North Holl and Biomedical Press Amsterdam
Cited by
Sorted by citations
King, A. C., Hasin, D., O’Connor, S. J., McNamara, P. J., & Cao, D. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.05.007 · Cited by 132 · see citing works
- Authors
- Matson, L. M., Kasten, C. R., Boehm, S. L., & Grahame, N. J.
- Affiliations
- Indiana University Indianapolis (US)
- Corresponding author
- Grahame, Nicholas J.
- Venue
- Alcoholism Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2013-08-01
- Volume
- 38
- Issue
- 1
- Pages
- 267-274
- ISSN
- 0145-6008 (ISSN-L)
- PMC
- PMC3844084
- OpenAlex
- W2134894690
- Cited by
- 38
- References
- 31
- Citations by year
- 2026: 2 · 2024: 4 · 2023: 2 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 3 · 2014: 4 · 2013: 2
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- IUScholarWorks (Indiana University) (submittedVersion)
- Purdue University Indianapolis (Indiana University) (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (T32 AA07462, P60 AA 07611, T32AA007462, P60AA007611)
- 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
- alcohol tolerance, locomotor sensitization, ethanol intoxication, ataxia, blood alcohol concentration, alcohol preference, alcoholism, chronic alcohol consumption, animal models of alcoholism
- MeSH terms
- Alcohol Drinking, Ethanol, Alcoholic Intoxication, Animals, Choice Behavior, Female, Hybridization, Genetic, Male, Motor Activity, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
