Environmental enrichment during adolescence heightens ethanol intake in female, but not male, adolescent rats that are selectively bred for high and low ethanol intake during adolescence

ABSTRACT

Background: Discriminating between adolescents who will eventually have ethanol use problems from those who do not is important. Environmental enrichment is a promising approach to reduce drug-related problems, but its impact on ethanol’s effects and intake is being scrutinized. Objective: We tested the effects of environmental enrichment on ethanol intake, preference, and anxiety-like response as well as shelter seeking and risk-taking behaviors.

Methods: Experiment 1 examined ethanol intake, preference, and anxiety-like responses in 46 male and 54 female Wistar rats that were derived from a short-term breeding program that selected for high and low ethanol drinking during adolescence (ADHI₂ and ADLO₂ lines, respectively). Shelter-seeking and risk-taking behaviors were assessed (Experiment 2) in ADHI₂ and ADLO₂ rats (73 males, 76 females) reared under environmental enrichment or standard housing conditions and given doses of ethanol (2.5 g/kg, intraperitoneal) for 3 weeks. Environmental enrichment was applied on postnatal days 21–42. Ethanol intake was measured on postnatal days 42–68. Anxiety-like behavior and exploratory responses were assessed using the light-dark box and multivariate concentric square field test.

Results: In Experiment 1, environmental enrichment increased ethanol intake in female, but not male, ADHI₂ and ADLO₂ rats (p < 0.05). In the baseline measurement of Experiment 2, ADHI₂ rats exhibited reduced risk-taking and increased anxiety-like behavior (p < .05). After exposure to environmental enrichment the ADHI and ADLO rats, both males and females, exhibited increased risk-taking and exploratory behavior (p < 0.05).

Conclusions: Environmental enrichment appears to increase ethanol intake in female rats by promoting the exploration of new environments or stimuli. The findings indicate that environmental enrichment increased ethanol intake in female, but not male, rats. Clinical programs that treat alcohol use disorder by emphasizing environmental stimulation should be designed with caution.

KEYWORDS:

• Ethanol
• short-term selection
• rat
• environmental enrichment

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Author’s contributors

Pautassi, Fernández, and Suárez designed the study. Pautassi, Suárez, Fabio, and Bellia performed the experimental procedures. Pautassi, Fabio, and Fernández conducted the statistical analysis. All of the authors prepared the first draft of the manuscript, revised the manuscript, and agreed to its submission for publication.

Disclosure statement

All of the authors declare that they have no conflicts of interest.

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Funding

This work was supported by grants from the Agencia Nacional de Promoción Científica y Técnica [FONCYT 2015-0325] and Universidad Nacional de Córdoba [SECyT-UNC] to Ricardo Pautassi. This work was also supported by Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET, Argentina). The funding agencies had no role in the study design, collection, analysis, and interpretation of data, writing the manuscript, or decision to submit the paper;Fondo para la Investigación Científica y Tecnológica [2015-0325];