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Binge drinking in male adolescent rats and its relationship to persistent behavioral impairments and elevated proinflammatory/proapoptotic proteins in the cerebellum

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Abstract

Rationale

To demonstrate that repeated episodes of binge drinking during the adolescent period can lead to long-term deficits in motor function and memory in adulthood, and increase proteins in the brain involved with inflammation and apoptotic cell death.

Methods

Groups of early adolescent (PND 26) and periadolescent (PND 34) Sprague-Dawley rats were exposed to either ethanol or plain air through a vapor chamber apparatus for five consecutive days (2 h per day), achieving a blood ethanol concentration equivalent to 6–8 drinks in the treatment group. Subjects then underwent a series of behavioral tests designed to assess memory, anxiety regulation, and motor function. Brains were collected on PND 94 for subsequent western blot analysis.

Results

Behavioral testing using the rota-rod, cage-hang, novel object recognition, light-dark box, and elevated plus maze apparatuses showed significant differences between groups; several of which persisted for up to 60 days after treatment. Western blot testing indicated elevated levels of caspase-3/cleaved caspase-3, NF-kB, and PKC/pPKC proteins in the cerebella of ethanol-treated animals.

Conclusions

Differences on anxiety tests indicate a possible failure of behavioral inhibition in the treatment group leading to riskier behavior. Binge drinking also impairs motor coordination and object memory, which involve the cerebellar and hippocampal brain regions, respectively. These experiments indicate the potential dangers of binge drinking while the brain is still developing and indicate the need for future studies in this area.

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Acknowledgements

We would like to thank Catherine Grandy and Steven Rowe for their contributions to behavioral experiments.

Funding

This work was funded in part by Canadian federal grants from the Natural Sciences and Engineering Research Council (NSERC; #RGPIN-2015-05389), the Canada Foundation for Innovation (CFI; project #16479), and the A.G. Hatcher Memorial Scholarship. Memorial University's Seed, Bridge and Multidisciplinary Fund

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Authors and Affiliations

  1. School of Pharmacy, Memorial University, Health Sciences Centre, 300 Prince Philip Drive, St. John’s, NL, A1B 3V6, Canada

    Matthew G. Lamont, Nicole Head & John T. Weber

  2. Department of Psychology, Memorial University, St. John’s, NL, Canada

    Phillip McCallum & Jacqueline Blundell

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  1. Matthew G. Lamont
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Correspondence to John T. Weber.

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Electronic supplementary material

Supplementary Fig. 1

There was no withdrawal effect on the subject’s propensity for locomotion (p = .11) or movement speed (p = .14) when this was measured using a simple open arena (n = 12 per group) (PNG 307 kb)

High resolution image (TIF 2446 kb)

Supplementary Fig. 2

There was no statistically significant difference seen between groups on the open field, acoustic startle, or fear conditioning tests (all p > .05; Supp. Fig. 2) (PNG 60 kb)

High resolution image (TIF 441 kb)

Supplementary Fig. 3

Relative amount of caspase-3 in the cerebral cortex of control versus ethanol-treated rats. No significant differences were noted (p = .82; n = 8 per group) (PNG 169 kb)

High resolution image (TIF 1196 kb)

Supplementary Fig. 4

Between-group comparison of the ratios of activated to base levels of the proteins examined in this study. No significant differences were noted; the closest was the comparison of caspase 3 proteins (p = .07; n = 8 per group) (PNG 408 kb)

High resolution image (TIF 3037 kb)

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Lamont, M.G., McCallum, P., Head, N. et al. Binge drinking in male adolescent rats and its relationship to persistent behavioral impairments and elevated proinflammatory/proapoptotic proteins in the cerebellum. Psychopharmacology 237, 1305–1315 (2020). https://doi.org/10.1007/s00213-020-05458-3

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  • DOI: https://doi.org/10.1007/s00213-020-05458-3

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