Animal models to study depression and antidepressants

Animal (e.g., mice) models to study depression (typically the forced swim test [FST], the tail suspension test [TST] and the sucrose preference test) are mostly based on the induction of biological or behavioural changes seen in people with MDD using a psychosocial or biophysical stressor.³ This is due to the widespread assumption that non-human animals are unable to experience depression in its phenomenological and biological entirety; however, they display behaviours similar to symptoms of MDD observed in humans.³ These depressive-like behaviours are induced by causative factors (e.g., environmental, genetic), can be quantified by standardized behavioural tests and should respond to established antidepressants.³ However, the relationship between the rodent behaviours in these tests and the symptoms of depression in humans is not obvious (i.e., they lack face validity).⁴

Animal models continue to be crucial for the study of depression.⁴ The translatability of findings from animal models of depression to humans with MDD can be improved by the application of clinical depression criteria along with Research Domain Criteria to provide a biobehavioral reference syndrome for rodent models of depression.³ A more sophisticated animal model of depression would be based on species-specific evidence such as minimum duration of depressive phenotype, significant sociofunctional impairment, core biological features of depression, and depressive-like symptoms (e.g., loss of energy or fatigue, lack of concentration or indecisiveness, psychomotor agitation or retardation, sleep disturbances, weight changes or diminished interest or pleasure in activities).³

References:

1. Abelaira HM, Réus GZ, Quevedo J. Animal models as tools to study the pathophysiology of depression. Braz J Psychiatry 2013; 35 (Suppl 2): S112–120.
2. Jensen KHR, Dam VH, Ganz M, et al. Deep phenotyping towards precision psychiatry of first-episode depression – the Brain Drugs-Depression cohort. BMC Psychiatry 2023; 23 (1): 151.
3. von Mücke-Heim I-A, Urbina-Treviño L, Bordes J, et al. Introducing a depression-like syndrome for translational neuropsychiatry: a plea for taxonomical validity and improved comparability between humans and mice. Mol Psychiatry 2023; 28: 329–340.
4. Bale TL, Abel T, Akil H, et al. The critical importance of basic animal research for neuropsychiatric disorders. Neuropsychopharmacol 2019; 44 (8): 1349–1353.