Opinion: Ethical Challenges in Depression Research: The Tail Suspension Test, the Forced Swim Test, and Alternative Behavioral Models

Behavioral tests in laboratory animals, particularly rodents, are considered vital for understanding the mechanisms underlying depression and evaluating potential treatments. However, ethical concerns regarding the use of traditional methods, such as the tail suspension test and the forced swimming test, which induce significant distress, have led to calls for more humane alternatives. In this paper we explore the ethical considerations surrounding common behavioral tests used in depression research, focusing on the tail suspension test’s and forced swimming test’s potential to cause harm to animals and their controversial relevance to human depression. Alternative methods, including the nest building behavior assessment and social interaction observations, provide valuable insights into depression-like behaviors without inducing unnecessary stress. We advocate for a shift toward mild-stress testing methods aligned with the 3Rs principle (replacement, reduction, and refinement). By integrating these humane practices, and promoting education on alternative methods, the scientific community can enhance the ethical integrity and translational relevance of preclinical depression research.