title: Validity Assessment of 5 Day Repeated Forced-Swim Stress to Model Human Depression in Young-Adult C57BL/6J and BALB/cJ Mice.
abstract: The development of animal models with construct, face, and predictive validity to accurately model human depression has been a major challenge. One proposed rodent model is the 5 d repeated forced swim stress (5d-RFSS) paradigm, which progressively increases floating during individual swim sessions. The onset and persistence of this floating behavior has been anthropomorphically characterized as a measure of depression. This interpretation has been under debate because a progressive increase in floating over time may reflect an adaptive learned behavioral response promoting survival, and not depression (Molendijk and de Kloet, 2015). To assess construct and face validity, we applied 5d-RFSS to C57BL/6J and BALB/cJ mice, two mouse strains commonly used in neuropsychiatric research, and measured a combination of emotional, homeostatic, and psychomotor symptoms indicative of a depressive-like state. We also compared the efficacy of 5d-RFSS and chronic social defeat stress (CSDS), a validated depression model, to induce a depressive-like state in C57BL/6J mice. In both strains, 5d-RFSS progressively increased floating behavior that persisted for at least 4 weeks. 5d-RFSS did not alter sucrose preference, body weight, appetite, locomotor activity, anxiety-like behavior, or immobility behavior during a tail-suspension test compared with nonstressed controls. In contrast, CSDS altered several of these parameters, suggesting a depressive-like state. Finally, predictive validity was assessed using voluntary wheel running (VWR), a known antidepressant intervention. Four weeks of VWR after 5d-RFSS normalized floating behavior toward nonstressed levels. These observations suggest that 5d-RFSS has no construct or face validity but might have predictive validity to model human depression.
authors.affiliation: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School , Boston, Massachusetts 02215.
authors.forename: Joram D
authors.identifier: 0000-0003-0453-2568
authors.initials: JD
authors.lastname: Mul
authors.affiliation: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School , Boston, Massachusetts 02215.
authors.forename: Jia
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215; Department of Medicine, Brigham, and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02215.
authors.forename: Laurie J
authors.initials: LJ
authors.lastname: Goodyear
mesh_terms: D059445:Anhedonia; D000818:Animals; D001007:Anxiety; D001835:Body Weight; D003866:Depressive Disorder / Q000209:etiology / Q000503:physiopathology; D019422:Dietary Sucrose; D004195:Disease Models, Animal; D004291:Dominance-Subordination; D005518:Food Preferences; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D013045:Species Specificity; D013315:Stress, Psychological / Q000150:complications; D013550:Swimming
chemical_list: D019422:Dietary Sucrose
keywords: anhedonia; animal model; depression; forced swimming; stress; voluntary wheel running