Rethinking data treatment: The sucrose preference threshold for anhedonia in stress-induced rat models of depression

Berrio, Jenny P.; Kalliokoski, Otto

doi:10.1016/j.jneumeth.2023.109910

Cited by 10 publications

(3 citation statements)

References 52 publications

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“…Thus misleading conclusions are reached that risk painting an inflated and unrealistic picture of the change in reward sensitivity. Especially when sucrose preference test results are used to discriminate between resilient and susceptible animals, a practice that in turn overestimates the effect, thus escalating the problem as demonstrated in our follow up study 38 . This has tremendous implications for the translatability and ethics of the research in the area 39 .…”

Section: Discussionmentioning

confidence: 91%

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

Berrio¹,

Kalliokoski²,

Hestehave³

2023

Preprint

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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 hours of food and/or water deprivation before the test. Sweet consumptions, for stressed and control/antidepressant-treated animals, in 132 studies were pooled in a random effects model. 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. 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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Section: Discussionmentioning

confidence: 91%

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

Berrio¹,

Kalliokoski²,

Hestehave³

2023

Preprint

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“…Even if the individual studies do not present hyperbolic findings, they muddy the waters, making truthful effects harder to gauge with any accuracy. In the context of preclinical depression studies, we already have to contend with evidence of publications bias 10 and exaggerated effects 55 . Fraudulent studies going along with these inflated effects ensure that erroneous findings become difficult, if not impossible, to overturn.…”

Section: Discussionmentioning

confidence: 99%

Fraudulent studies are undermining the reliability of systematic reviews – a study of the prevalence of problematic images in preclinical studies of depression

Berrío,

Kalliokoski

2024

Preprint

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Systematic reviews are considered by many to constitute the highest level of scientific evidence. A caveat is that the methods used in a systematic review - combining information from multiple studies - are predicated on all of the reports being truthful. Currently, we do not know how frequent fraudulent studies are in systematic reviews, or how they affect the resulting evidence base. For a systematic review of preclinical studies of depression, we found that potentially fraudulent studies were not only common but also that they biased the findings of the review. In a sample of 1,035 studies, we found that 19 % of peer-reviewed reports displayed data in the form of problematic images. In a majority of the cases, images had been altered or recycled in a way that makes us suspect foul play. Making things worse, these studies reported larger effect sizes, on average, than did studies where we did not identify problems. Counter to commonly held beliefs, reports with problematic images were not cited less or published in lower-impact journals, nor were their authors isolated to any specific geographic area. The sheer prevalence of problematic studies, and the fact that we could not find a simple pattern for identifying them, undermines the validity of systematic reviews within our research field. We suspect that this is symptomatic of a broader problem that needs immediate addressing.

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“…Rats could be deprived of food and water before the experiment. The concentration of sucrose usually ranges between 0.5% and 2%, with the duration of the test varying from 15 min to 8 days [92].…”

Section: Investigation Of Behavioral and Cognitive Functions In Ratsmentioning

confidence: 99%

Behavioral and Cognitive Comorbidities in Genetic Rat Models of Absence Epilepsy (Focusing on GAERS and WAG/Rij Rats)

Sitnikova

2024

Biomedicines

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Absence epilepsy is a non-convulsive type of epilepsy characterized by the sudden loss of awareness. It is associated with thalamo-cortical impairment, which may cause neuropsychiatric and neurocognitive problems. Rats with spontaneous absence-like seizures are widely used as in vivo genetic models for absence epilepsy; they display behavioral and cognitive problems similar to epilepsy in humans, such as genetic absence epilepsy rats from Strasbourg (GAERS) and Wistar Albino rats from Rijswijk (WAG/Rij). Depression- and anxiety-like behaviors were apparent in GAERS, but no anxiety and depression-like symptoms were found in WAG/Rij rats. Deficits in executive functions and memory impairment in WAG/Rij rats, i.e., cognitive comorbidities, were linked to the severity of epilepsy. Wistar rats can develop spontaneous seizures in adulthood, so caution is advised when using them as a control epileptic strain. This review discusses challenges in the field, such as putative high emotionality in genetically prone rats, sex differences in the expression of cognitive comorbidities, and predictors of cognitive problems or biomarkers of cognitive comorbidities in absence epilepsy, as well as the concept of “the cognitive thalamus”. The current knowledge of behavioral and cognitive comorbidities in drug-naive rats with spontaneous absence epilepsy is beneficial for understanding the pathophysiology of absence epilepsy, and for finding new treatment strategies.

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Rethinking data treatment: The sucrose preference threshold for anhedonia in stress-induced rat models of depression

Cited by 10 publications

References 52 publications

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

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

Fraudulent studies are undermining the reliability of systematic reviews – a study of the prevalence of problematic images in preclinical studies of depression

Behavioral and Cognitive Comorbidities in Genetic Rat Models of Absence Epilepsy (Focusing on GAERS and WAG/Rij Rats)

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