Maternal separation stress in male mice: long-term increases in alcohol intake
Open accessAbstract
Rationale In rodents, prolonged maternal separation has been used as a model of developmentally early environmental stress to influence adult drug intake. Objectives The aim of the present study was to evaluate the long-term effects of prolonged maternal separation on alcohol consumption using two different self-administration procedures in mice: operant alcohol self-administration vs. three-bottle choice. Materials and methods From postnatal day (PND) 1 to 14, pups were separated from the dam (maternal separation, MS) daily for 180 min or were left undisturbed, only handled during cage cleaning (animal facility rearing, AFR). On PND 60, they were assigned to one of two experimental manipulations: either a three-bottle choice or operant oral alcohol self-administration. In the three-bottle choice procedure, mice were given access to 6% or 10% alcohol or 0.05% saccharin solution for 2 h/day for 10 days. In the second experiment, mice were reinforced for nose poking by delivery of oral alcohol (6% or 10% in saccharin) or 0.05% saccharin solutions during daily 30-min sessions. Following the acquisition phase, "break points" were determined. Later, mice were allowed 1 h access to the reinforcing solution with no dosage limitation. Results In the three-bottle choice procedure, MS mice showed higher alcohol intake than AFR at the 10% alcohol concentration. In the operant alcohol self-administration, MS mice achieved higher alcohol intake than AFR at the concentrations 6% and 10% during the 1-h session. Conclusions The results demonstrate the long-term consequences of MS on alcohol intake in male mice, suggesting early life stress as a risk factor for alcohol consumption and abuse.
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In CFW male mice, three hours of maternal separation for the first two weeks after birth increases alcohol consumption compared to those left undisturbed in early life.
“In CFW male mice, those commonly used for studying alcohol-heightened aggression, three hours of MS for the first two weeks after birth increases alcohol consumption compared to those left undisturbed in early life (Cruz et al. 2008).”
From Decoding the bidirectional links between alcohol misuse and aggression: toward a unified translational framework (2026) · cites this paper as Cruz et al. 2008
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- Authors
- Cruz, F. C., Quadros, I. M., da S. Planeta, C., & Miczek, K. A.
- Affiliations
- Tufts University (US)
- Corresponding author
- Miczek, Klaus A.
- Venue
- Psychopharmacology
- Published
- 2008-09-03
- Volume
- 201
- Issue
- 3
- Pages
- 459-468
- ISSN
- 0033-3158 (ISSN-L)
- 1432-2072
- PMC
- PMC4367178
- OpenAlex
- W2059330727
- Cited by
- 109
- References
- 62
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 5 · 2023: 7 · 2022: 4 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 12 · 2017: 3 · 2016: 12 · 2015: 5 · 2014: 3 · 2013: 9 · 2012: 8
- FWCI
- 3.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Psychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Acervo Digital da Universidade Estadual Paulista (Universidade Estadual Paulista) (submittedVersion)
- UNESP Institutional Repository (São Paulo State University) (submittedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA013983, AA0013983)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- maternal separation, early life stress, alcohol self-administration, alcohol consumption, male mice, alcohol abuse risk, developmental stress
- MeSH terms
- Alcohol Drinking, Ethanol, Animals, Animals, Newborn, Behavior, Animal, Choice Behavior, Conditioning, Operant, Drinking, Female, Male, Maternal Deprivation, Reinforcement, Psychology, Stress, Psychological, Time Factors, Animals, Outbred Strains, Mice
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