This dissertation examines how academic neuroscientists working with rat and mouse models of depression, anxiety, and post-traumatic stress disorder (PTSD) discuss the value of animal research. Since the mid-2000s, the field of animal experimentation has undergone changes as researchers published several studies addressing neuroscience’s challenges with replicating and translating animal research. Around this time, major pharmaceutical companies stopped pursuing a more robust pipeline for new psychopharmaceuticals, citing the lack of major discoveries since the selective serotonin reuptake inhibitor (SSRI) boom of the 1990s. Drawing on eighteen months of ethnographic fieldwork with academic neuroscientists, postdoctoral students, laboratory technicians, and graduate students, this dissertation explores how researchers viewed their work in the context of these dynamics as they raised uncertainties about the value of animal models and what they model. It describes how they questioned how to model psychiatric diagnoses in rodents, especially when these diagnoses lack discrete biological markers in both humans and animals. It also follows how researchers navigated their field’s injunction to avoid anthropomorphizing animals. For example, they displayed restraint from attributing human-like qualities to animals while they modeled emotions in them. They also argued that aspects of animals’ emotional experiences might be unknowable to science and that animals might not consciously experience certain emotions in the first place. In equating restraint from anthropomorphism with an ideal of scientific objectivity, they created more uncertainty in a prescribed mode of objectivity. Such uncertainty about what models represent and whether rodents consciously experience emotions allowed researchers to bracket potentially uncomfortable conversations about animal suffering. This dissertation tracks how researchers position animals as tools of science while simultaneously raising questions about what they model. In doing so, it raises questions about how animal research involves inevitable harms to animals, as well as the uncertain cost-benefit calculations we all undertake when weighing whether our methods of observation are worth it.