The sucrose preference test (SPT) is a reward-based test, used as in indicator of anhedonia. Anhedonia, or the decreased ability to experience pleasure, represents one of the core symptoms of depression. Rodents are born with an interest in sweet foods or solutions. Reduced preference for sweet solution in SPT represents anhedonia, while this reduction can be reversed by treatment with antidepressants. SPT is carried out in the animal’s home cage. For the SPT, mice are presented with 2 dual bearing sipper tubes. One tube contains plain drinking water, and the second contains a sucrose solution. Water and sucrose solution intake is measured daily, and the positions of two bottles is switched daily to reduce any confound produced by a side bias. Sucrose preference is calculated as a percentage of the volume of sucrose intake over the total volume of fluid intake and averaged over the testing period. Here, we present our protocol that has been able to detect anhedonia in mice subjected to a chronic depression model.

The 2-bottle choice procedure for assessing sucrose preference is a useful test to investigate anhedonia (i.e., inability to feel pleasure) in laboratory rodents, particularly in stress-based models of depression. The 2-bottle choice procedure allows for a comparison between behavioral preference for sucrose solution in drinking water compared to water only. Preference is measured by volume and/or weight of liquid consumed daily, which is then converted to a percent preference compared to a water only baseline period. Sucrose preference is attenuated by a diversity of chronic stressors, including chronic mild and unpredictable stress (Willner et al., 1992; Willner, 1997; Pothion et al., 2004) and social defeat stress (Krishnan et al., 2007). It may also be susceptible to perturbation in mouse models of drug addiction because sucrose preference is altered in drug-dependent individuals (Kampov-Polevoy et al., 1997; Bogucka-Bonikowska et al., 2002; Janowsky et al., 2003). Both stress- and drug-induced alterations in sucrose preference may stem from maladaptations in the reward pathway, which consists of the dopaminergic neurons extending from the ventral tegmental area to the nucleus accumbens (NAc). Indeed, alterations in cyclic-AMP response element binding protein (CREB) activity in NAc underlie preference for sucrose (Barrot et al., 2002). Additionally, the transcription factor ΔFosB in NAc (Wallace et al., 2008), but not dorsal hippocampus (Eagle et al., 2015), regulates natural rewards, such as sucrose consumption. Therefore, the sucrose preference test described below provides a well-validated model to assess anhedonia and the function of specific brain regions and circuits.