Adolescent intermittent ethanol exposure induces sex‐dependent divergent changes in ethanol drinking and motor activity in adulthood in C57BL/6J mice
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Abstract
With alcohol readily accessible to adolescents, its consumption leads to many adverse effects, including impaired learning, attention, and behavior. Adolescents report higher rates of binge drinking compared to adults. They are also more prone to substance use disorder in adulthood due to physiological changes during the adolescent developmental period. We used C57BL/6J male and female mice to investigate the long‐lasting impact of binge ethanol exposure during adolescence on voluntary ethanol intake and open field behavior during later adolescence (Experiment 1) and during emerging adulthood (Experiment 2). The present set of experiments were divided into four stages: (1) adolescent intermittent vapor inhalation exposure, (2) abstinence, (3) voluntary ethanol intake, and (4) open field behavioral testing. During adolescence, male and female mice were exposed to air or ethanol using intermittent vapor inhalation from postnatal day (PND) 28–42. Following this, mice underwent short‐term abstinence from PND 43–49 (Experiment 1) or protracted abstinence from PND 43–69 (Experiment 2). Beginning on PND 50–76 or PND 70–97, mice were assessed for intermittent voluntary ethanol consumption using a two‐bottle choice drinking procedure over 28 days. Male adolescent ethanol‐exposed mice showed increased ethanol consumption following short‐term abstinence and following protracted abstinence. In contrast, female mice showed no changes in ethanol consumption following short‐term abstinence and decreased ethanol consumption following protracted abstinence. There were modest changes in open field behavior following voluntary ethanol consumption in both experiments. These data demonstrate a sexually divergent shift in ethanol consumption following binge ethanol exposure during adolescence and differences in open field behavior. These results highlight sex‐dependent vulnerability to developing substance use disorders in adulthood.
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Adolescent alcohol exposure increases future alcohol consumption in rodents and humans.
“AAE also increases future alcohol consumption in rodents [32, 33], as well as humans [34].”
From Consequences of adolescent drug use (2023) · cites this paper as [33]
The Results (Experiment 2, page not available) report increased ethanol consumption in adolescent-exposed male mice but decreased consumption in female mice. Thus the source supports the rodent claim for males, not rodents generally. The sentence cites a different source for the human claim. (LLM, conf=0.88)
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Cites
The adolescent brain and age-related behavioral manifestations
Spear, L. P. (2000) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(00)00014-2 · Cited by 5,433 · see citing works
Results From the 2008 National Survey on Drug Use and Health: National Findings
(2009) · PsycEXTRA Dataset · doi:10.1037/e592592009-001 · Cited by 1,178 · see citing works
Methods of Behavior Analysis in Neuroscience
(2008) · CRC Press eBooks · doi:10.1201/9780367802622 · Cited by 777 · see citing works
Thigmotaxis as an index of anxiety in mice. Influence of dopaminergic transmissions
Simon, P. Y. R., Dupuis, R., & Costentin, J. (1994) · Behavioural Brain Research · doi:10.1016/0166-4328(94)90008-6 · Cited by 767 · see citing works
Neurobiology of the Adolescent Brain and Behavior: Implications for Substance Use Disorders
Casey, B. J., & Jones, R. M. (2010) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2010.08.017 · Cited by 692 · see citing works
Age at first drink and the first incidence of adult-onset DSM-IV alcohol use disorders
Dawson, D. A., Goldstein, R. B., Patricia Chou, S., June Ruan, W., & Grant, B. F. (2008) · Alcoholism: Clinical and Experimental Research · doi:10.1111/j.1530-0277.2008.00806.x · Cited by 548 · see citing works
Becker, H. C., & Lopez, M. F. (2004) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000149977.95306.3a · Cited by 419 · see citing works
Pascual, M., Boix, J., Felipo, V., & Guerri, C. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05835.x · Cited by 318 · see citing works
Factors influencing elevated ethanol consumption in adolescent relative to adult rats
Doremus, T. L., Brunell, S. C., Rajendran, P., & Spear, L. P. (2005) · Alcoholism: Clinical & Experimental Research · doi:10.1097/01.alc.0000183007.65998.aa · Cited by 291 · see citing works
Anxiety-Related Behaviors in Mice
Crawley, J. N., & Bailey, K. (2008) · Frontiers in neuroscience · doi:10.1201/noe1420052343.ch5 · Cited by 266 · see citing works
Tatem, K. S., Quinn, J. L., Phadke, A., Yu, Q., Gordish‐Dressman, H., & Nagaraju, K. (2014) · Journal of Visualized Experiments · doi:10.3791/51785 · Cited by 256 · see citing works
Lopez, M. F., & Becker, H. C. (2005) · Psychopharmacology · doi:10.1007/s00213-005-0026-3 · Cited by 248 · see citing works
Gass, J. T., Glen, W. B., McGonigal, J. T., Trantham-Davidson, H., Lopez, M. F., Randall, P. K., Yaxley, R., Floresco, S. B., & Chandler, L. J. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.109 · Cited by 197 · see citing works
Vapor Inhalation of Alcohol in Rats
Gilpin, N., Richardson, H. N., Cole, M., & Koob, G. (2008) · Current Protocols in Neuroscience · doi:10.1002/0471142301.ns0929s44 · Cited by 186 · see citing works
Patrick, M. E., Schulenberg, J. E., O’Malley, P. M., Johnston, L. D., & Bachman, J. G. (2011) · Journal of Studies on Alcohol and Drugs · doi:10.15288/jsad.2011.72.106 · Cited by 183 · see citing works
Miller, R. S., Sweeney, S. J., Slootmaker, C., Grear, D. A., Salvo, P. A. D., Kiser, D., & Shwiff, S. A. (2017) · Scientific Reports · doi:10.1038/s41598-017-07336-z · Cited by 183 · see citing works
Alaux‐Cantin, S., Warnault, V., Legastelois, R., Botia, B., Pierrefiche, O., Vilpoux, C., & Naassïla, M. (2012) · Neuropharmacology · doi:10.1016/j.neuropharm.2012.12.007 · Cited by 167 · see citing works
Crews, F. T., Robinson, D. L., Chandler, L. J., Ehlers, C. L., Mulholland, P. J., Pandey, S. C., Rodd, Z. A., SPEAR, L. P., Swartzwelder, H. S., & Vetreno, R. P. (2019) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14154 · Cited by 166 · see citing works
Gilpin, N. W., Karanikas, C. A., & Richardson, H. N. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031466 · Cited by 146 · see citing works
New replicable anxiety-related measures of wall vs. center behavior of mice in the open field
Lipkind, D., Sakov, A., Kafkafi, N., Elmer, G. I., Benjamini, Y., & Golani, I. (2004) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00148.2004 · Cited by 143 · see citing works
A Human Open Field Test Reveals Thigmotaxis Related to Agoraphobic Fear
Walz, N., Mühlberger, A., & Pauli, P. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.12.016 · Cited by 140 · see citing works
Griffin, W. C., Lopez, M. F., Yanke, A. B., Middaugh, L. D., & Becker, H. C. (2008) · Psychopharmacology · doi:10.1007/s00213-008-1324-3 · Cited by 136 · see citing works
Sex differences in the behavioral sequelae of chronic ethanol exposure
Jury, N. J., DiBerto, J. F., Kash, T. L., & Holmes, A. (2016) · Alcohol · doi:10.1016/j.alcohol.2016.07.007 · Cited by 116 · see citing works
Automated measurement of spatial preference in the open field test with transmitted lighting
Kulikov, V. A., Tikhonova, M. A., & Kulikov, V. A. (2008) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2008.01.024 · Cited by 113 · see citing works
Tambour, S., Brown, L. L., & Crabbe, J. C. (2008) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2008.00798.x · Cited by 105 · see citing works
Effect of sex on ethanol consumption and conditioned taste aversion in adolescent and adult rats
Schramm‐Sapyta, N. L., Francis, R., MacDonald, A. L., Keistler, C., O’Neill, L., & Kuhn, C. M. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3319-y · Cited by 101 · see citing works
Trantham‐Davidson, H., Centanni, S. W., Garr, S. C., New, N., Mulholland, P. J., Gass, J. T., Glover, E. J., Floresco, S., Crews, F. T., Krishnan, H. R., et al. (2016) · Neuropsychopharmacology · doi:10.1038/npp.2016.190 · Cited by 100 · see citing works
Lopez, M. F., & Laber, K. (2014) · Physiology & Behavior · doi:10.1016/j.physbeh.2014.11.012 · Cited by 87 · see citing works
Ehlers, C. L., Liu, W., Wills, D. N., & Crews, F. T. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.03.058 · Cited by 83 · see citing works
Long‐Term Neurobehavioral Effects of Alcohol or Nicotine Exposure in Adolescent Animal Models
Slawecki, C. J., Thorsell, A., & Ehlers, C. L. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1308.062 · Cited by 82 · see citing works
Morales, M., McGinnis, M. M., & McCool, B. A. (2015) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2015.10.016 · Cited by 78 · see citing works
Effects of adolescent ethanol exposure on ethanol consumption in adult rats
Slawecki, C. J., & Betancourt, M. (2002) · Alcohol · doi:10.1016/s0741-8329(01)00192-6 · Cited by 74 · see citing works
Rivera-Irizarry, J. K., Skelly, M. J., & Pleil, K. E. (2020) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2020.00129 · Cited by 72 · see citing works
List of transgenic and knockout mice: behavioral profiles
Bolivar, V. J., Cook, M. N., & Flaherty, L. A. (2000) · Mammalian Genome · doi:10.1007/s003350010051 · Cited by 71 · see citing works
Diaz‐Granados, J. L., & Graham, D. L. (2007) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2007.00534.x · Cited by 70 · see citing works
Maldonado‐Devincci, A. M., Alipour, K. K., Michael, L. A., & Kirstein, C. L. (2010) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2010.07.008 · Cited by 70 · see citing works
Self-citationAmodeo, L. R., Wills, D. N., Sánchez-Alavez, M., Nguyen, W., Conti, B., & Ehlers, C. L. (2018) · Alcohol · doi:10.1016/j.alcohol.2018.04.003 · Cited by 69 · see citing works
Dhaher, R., Finn, D. A., Snelling, C., & HITZEMANN, R. J. (2007) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2007.00566.x · Cited by 67 · see citing works
Amodeo, L. R., Kneiber, D., Wills, D. N., & Ehlers, C. L. (2017) · Alcohol · doi:10.1016/j.alcohol.2016.12.002 · Cited by 65 · see citing works
Walker, B. M., Drimmer, D. A., Walker, J. L., Liu, T., Mathé, A. A., & Ehlers, C. L. (2010) · Alcohol · doi:10.1016/j.alcohol.2010.06.006 · Cited by 63 · see citing works
Intermittent access to beer promotes binge-like drinking in adolescent but not adult Wistar rats
Hargreaves, G. A., Monds, L. A., Gunasekaran, N., Dawson, B., & McGregor, I. S. (2009) · Alcohol · doi:10.1016/j.alcohol.2009.02.005 · Cited by 47 · see citing works
Barker, J. M., Bryant, K. G., Osborne, J. I., & Chandler, L. J. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00450 · Cited by 46 · see citing works
Centanni, S. W., Burnett, E. J., Trantham‐Davidson, H., & Chandler, L. J. (2016) · Addiction Biology · doi:10.1111/adb.12353 · Cited by 44 · see citing works
Dannenhoffer, C. A., Kim, E. U., Saalfield, J., Werner, D. F., Varlinskaya, E. I., & SPEAR, L. P. (2018) · Psychopharmacology · doi:10.1007/s00213-018-5003-8 · Cited by 43 · see citing works
Kasten, C. R., Carzoli, K. L., Sharfman, N. M., Henderson, T., Holmgren, E. B., Lerner, M. R., Miller, M. C., & Wills, T. A. (2020) · Neuropsychopharmacology · doi:10.1038/s41386-020-0670-7 · Cited by 43 · see citing works
Acevedo, M. B., Molina, J. C., Nizhnikov, M. E., Spear, N. E., & Pautassi, R. M. (2010) · Developmental Psychobiology · doi:10.1002/dev.20444 · Cited by 42 · see citing works
Acheson, S., Bearison, C., Risher, M., Abdelwahab, S. H., Wilson, W. A., & Swartzwelder, H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0077768 · Cited by 41 · see citing works
Day, A. M., Celio, M. A., Lisman, S. A., Johansen, G. E., & SPEAR, L. P. (2013) · Journal of Studies on Alcohol and Drugs · doi:10.15288/jsad.2013.74.635 · Cited by 40 · see citing works
Alcohol Consumption in Adolescence: a Translational Perspective
SPEAR, L. P. (2016) · Current Addiction Reports · doi:10.1007/s40429-016-0088-9 · Cited by 40 · see citing works
Chang, P., Chow, D. S., Alber, A., Lin, Y., & Youn, Y. (2020) · Brain Sciences · doi:10.3390/brainsci10120991 · Cited by 40 · see citing works
Withdrawal Severity After Chronic Intermittent Ethanol in Inbred Mouse Strains
Metten, P., Sorensen, M. L., Cameron, A. J., Yu, C.-H., & Crabbe, J. C. (2010) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2010.01240.x · Cited by 39 · see citing works
McCool, B. A., & Chappell, A. M. (2015) · Alcohol · doi:10.1016/j.alcohol.2015.01.003 · Cited by 36 · see citing works
Nentwig, T. B., Starr, E. M., Chandler, L. J., & Glover, E. J. (2019) · Alcohol · doi:10.1016/j.alcohol.2019.01.006 · Cited by 36 · see citing works
Younis, R. M., Wolstenholme, J. T., Bağdaş, D., Bettinger, J. C., Miles, M. F., & Damaj, M. I. (2019) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2019.172740 · Cited by 35 · see citing works
Carrara‐Nascimento, P. F., Lopez, M. F., Becker, H. C., Olive, M. F., & Camarini, R. (2013) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.12056 · Cited by 29 · see citing works
Alcohol Binge Drinking and Anxiety‐Like Behavior in Socialized Versus Isolated C57BL/6J Mice
Evans, O., Rodríguez‐Borillo, O., Font, L., Currie, P. J., & Pastor, R. (2019) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14236 · Cited by 29 · see citing works
Rath, M., Guergues, J., Pinho, J. P. C., Zhang, P., Nguyen, T. G., MacFadyen, K. A., Peris, J., McLaughlin, J. P., Stevens, S. M., & Liu, B. (2020) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14420 · Cited by 29 · see citing works
Lopez, M. F., Miles, M. F., Williams, R. W., & Becker, H. C. (2016) · Alcohol · doi:10.1016/j.alcohol.2016.09.003 · Cited by 26 · see citing works
Incubation of Negative Affect during Protracted Alcohol Withdrawal Is Age-, but Not Sex-Selective
Chavez, C. L. J., Coelho, M. A., Brewin, L. W., Swauncy, I., Tran, T., Albanese, T., Laguna, A., Gabriela, I., & Szumlinski, K. K. (2020) · Brain Sciences · doi:10.3390/brainsci10060405 · Cited by 18 · see citing works
Maldonado‐Devincci, A. M., Kampov-Polevoi, A., McKinley, R. E., Morrow, D., O’Buckley, T. K., & Morrow, A. L. (2016) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2016.00040 · Cited by 17 · see citing works
Self-citationSalguero, A., Suárez, A. B., Luque, M., Ruíz-Leyva, L., Cendán, C. M., Morón, I., & Pautassi, R. M. (2020) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2020.00050 · Cited by 17 · see citing works
Miller, K. M., Risher, M., Acheson, S. K., Darlow, M., Sexton, H. G., Schramm‐Sapyta, N. L., & Swartzwelder, H. S. (2017) · Scientific Reports · doi:10.1038/s41598-017-04704-7 · Cited by 15 · see citing works
Cook, J. B., Nelli, S., Neighbors, M. R., Morrow, D. H., O'Buckley, T., Maldonado-Devincci, A. M., & Morrow, A. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.46 · Cited by 13 · see citing works
Self-citationGalaj, E., Barrera, E. D., Morris, D., Ma, Y., & Ranaldi, R. (2020) · Alcoholism Clinical and Experimental Research · doi:10.1111/acer.14341 · Cited by 6 · see citing works
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Consequences of adolescent drug use
Steinfeld, M. R., & Torregrossa, M. M. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02590-4 · Cited by 237 · see citing works
“AAE also increases future alcohol consumption in rodents [32, 33], as well as humans [34].”
Background
- Authors
- Maldonado‐Devincci, A. M., Makdisi, J. G., Hill, A. M., Waters, R. C., Hall, N. I., Shobande, M. J., & Kumari, A.
- Affiliations
- North Carolina Agricultural and Technical State University (US)
- Georgia State University (US)
- Department of Psychology College of Health and Human Sciences North Carolina Agricultural and Technical State University Greensboro NC USA
- Georgetown University (US)
- Corresponding author
- Maldonado‐Devincci, Antoniette M.
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2021-03-16
- Volume
- 100
- Issue
- 8
- Pages
- 1560-1572
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- PMC
- PMC8957701
- OpenAlex
- W3137733044
- Cited by
- 21
- References
- 64
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 3 · 2023: 6 · 2022: 2 · 2021: 4 · 2020: 1
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Journal of Neuroscience Research (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- adolescent intermittent ethanol exposure, binge drinking, sex differences, voluntary ethanol consumption, alcohol abstinence, emerging adulthood, open field behavior, motor activity, adolescent alcohol exposure, C57BL/6J mice
- MeSH terms
- Age Factors, Alcohol Drinking, Ethanol, Animals, Female, Male, Mice, Inbred C57BL, Motor Activity, Mice
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