An Updated Bio-Behavioral Profile of the Flinders Sensitive Line Rat: Reviewing the Findings of the Past Decade

The Flinders sensitive line (FSL) rat is an accepted rodent model for depression that presents with strong face, construct, and predictive validity, thereby making it suitable to investigate novel antidepressant mechanisms. Despite the translatability of this model, available literature on this model has not been reviewed for more than ten years. The PubMed, ScienceDirect and Web of Science databases were searched for relevant articles between 2013 and 2024, with keywords relating to the Flinders line rat, and all findings relevant to treatment naïve animals, included. Following screening, 77 studies were included and used to create behavioral reference standards and calculate FSL favor ratios for the various behavioral parameters. The GRADE and SYRCLE risk of bias tools were used to scale the quality of these studies. Based on these results, FSL rats display reliable and reproducible depressive-like behavior in the forced swim test, together with hyperlocomotor activity across various behavioral tests. Despite reports of increased anhedonia, anxiety-like behavior, and cognitive dysfunction, the reviewed findings indicate that these parameters are comparable between strains. For the various neuro- and biological constructs, oxidative stress, energy production, and glutamatergic, noradrenergic and serotonergic neurotransmission received the most support for strain differences. Taken together, the FSL remains a reliable, popular, and translatable rodent model of depression, with strong face and construct validity. As for predictive validity, similar review approaches should be considered to establish whether the mentioned behavioral aspects and neurochemical constructs may be more sensitive (or resistant) to certain antidepressant strategies.