How the Sucrose Preference Succeeds or Fails as a Measurement of Anhedonia

The sucrose preference test is used in laboratory rodents as a reward-based test to indicate a decrease in the sensitivity to a reward (anhedonia), which is a key symptom of major depression. It is based on the animal’s natural preference for sweets, with the assumption that this preference is in proportion to the pleasure that the animal experiences when it consumes sweetened solutions. As such, a reduction in the intake and preference of a sucrose-sweetened solution in rodents, typically compared to plain water over a fixed time frame, is considered as a manifestation of anhedonia. Despite the seemingly technical simplicity of the test, many laboratories experience serious difficulties in establishing this method in a sufficiently reproducible manner, especially in mice. Moreover, while a manifestation of anhedonia in the sucrose test parallels other depressive-like changes in rodents, the stratification of animals upon their hedonic responses as anhedonic and non-anhedonic is often problematic. Here, we address the most common technical, physical, and physiological phenomena that typically confound the evaluation of hedonic sensitivity with the sucrose test in laboratory mice and rats. The impact of these factors is often underestimated or neglected in routine laboratory work. When taken under control, however, the accuracy and sensitivity of the test is substantially increased and the abovementioned limitations with this method are resolved.