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

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 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.

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

“…A study that assessed sucrose consumption and self-stimulation thresholds in the same groups of animals failed to show that a decreased sucrose intake following chronic stress is accompanied by an increased intracranial self-stimulation 46 . In our review 6 , we found evidence of non-hedonic factors driving the consumption of sweet solutions. What is more, we observed that methodological strategies, meant to reduce bias when conducting the test (for example diminishing the effect of side preference on the test results), were often not implemented or not reported on.…”

“…It is not uncommon to find two studies with differing durations in fasting before the test, length of the test itself, or the concentration and type of the sweet solution employed. In our review, we found the sucrose concentration to range from 0.2% to 30% (w/v) and the length of test from 15 minutes to 8 days 6 . Different sucrose concentrations and test durations were also employed in the studies that are the center of the present paper (Table 1).…”

“…The chronic unpredictable stress model of depression, while popular, has a disadvantage in that the smallest changes in the methodology can cause great variability in the observed sweet consumption 5,42 . Differences in stress protocols and flexibility in testing methods, particularly in the case of sucrose preference testing, has led to high heterogeneity in the phenotype of the model 6,43 . It is not uncommon to find two studies with differing durations in fasting before the test, length of the test itself, or the concentration and type of the sweet solution employed.…”

“…This is an unlikely scenario from our point of view. In our systematic review we analyzed studies reporting little to no change in sweet preference after stress 6 . In some studies the preference for sucrose even increased 51,52 Even in this ideal scenario, we risk overestimating the effect of stress as explained above.…”

“…We focused on studies that used no fasting, or only short periods of food and/or water deprivation, before the test. These studies constituted only 18.3% of the total studies we found during our search that used the model 6 . In 18 of the 159 studies, the authors set a criterion for defining anhedonia.…”