Ethical considerations are central in designing experiments using animal models in neuroscience and psychiatry. Indeed, the treatment of laboratory animals should be done considering that animals, and particularly laboratory rodents, are sentient living beings that have needs to be fulfilled and the capacity to feel emotion, pain, and suffering. Accordingly, designing experiments using animals in neuroscience and psychiatry should follow several ethical recommendations like the three Rs (Replace, Reduce, Refine) and be validated by ethical committees. However, it happens than some ethical recommendations, when applied too drastically, can result in counterintuitive non-ethical outcomes, as in the example of the reduction/power tradeoff dilemma. We will discuss the outcomes of some examples of “ethical” and “experimental” practices when designing animal studies in the neurosciences and psychiatry, and propose recommendations for improving experimental designs and more ethical uses of laboratory animals.