Reliability of sucrose preference testing following short or no food and water deprivation—a Systematic Review and Meta-Analysis of rat models of chronic unpredictable stress
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Abstract
The sucrose preference test is a popular test for anhedonia in the chronic unpredictable stress model of depression. Yet, the test does not always produce consistent results. Long food and water deprivation before the test, while often implemented, confounds the results by introducing unwanted drives in the form of hunger and thirst. We assessed the reliability of the test when only short or no fasting was used. We searched PubMed, Embase, and Web of Science for studies in rats exposed to chronic unpredictable stress that used no more than 6 h of food and/or water deprivation before the test. Sweet consumptions, for stressed and control/antidepressant-treated animals, in 132 studies were pooled using random effects models. We found a decrease in sweet consumption in stressed rats, compared to controls, that was halved when a non-caloric sweetener was used and significantly reduced when sucrose consumption was corrected for body weight. What is more, the length of food and water deprivation was found to confound the effect. The effect was reversed when the stressed rats were treated with antidepressants. Methodological strategies meant to control for recognized sources of bias when conducting the test were often missing, and so was a clear and complete report of essential study information. Our results indicate that not only is food and water deprivation before the test unnecessary, but not recommended. Even in absence of long fasting, we found evidence of an additional effect on sweet consumption that is unrelated to anhedonia. Without properly controlling for non-hedonic drivers of consumption, the test is unreliable as a proxy measure of anhedonia. Strengthening the methodological rigor and addressing the confounding effect of metabolic factors in the sucrose preference test prevents misleading conclusions that harm the translatability of the associated research and perpetuates the use of animals for little gain.
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The unpredictable chronic stress model in laboratory rats is used to model depression.
“Our systematic review concerned unpredictable chronic stress, and its use in modelling depression in laboratory rats 10 .”
From Fraudulent studies are undermining the reliability of systematic reviews: on the prevalence of problematic images in preclinical depression studies (2025) · cites this paper as [10]
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- Authors
- Berrio, J. P., Hestehave, S., & Kalliokoski, O.
- Affiliations
- University College London (GB)
- University of Copenhagen (DK)
- Venue
- Translational Psychiatry
- Published
- 2024-01-19
- Volume
- 14
- Issue
- 1
- Pages
- 39-39
- ISSN
- 2158-3188 (ISSN-L)
- PMC
- PMC10799054
- OpenAlex
- W4391025772
- Cited by
- 49
- References
- 46
- Citations by year
- 2026: 16 · 2025: 20 · 2024: 9 · 2023: 4
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Translational Psychiatry (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Food and Agriculture
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- sucrose preference test, anhedonia, chronic unpredictable mild stress, animal models of depression, food and water deprivation, test reliability, artificial sweeteners, antidepressant treatment, rat model, confounding
- MeSH terms
- Animals, Food, Stress, Psychological, Sucrose, Water Deprivation, Reproducibility of Results, Rats, Anhedonia
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