Comorbid sensorimotor and emotional profiles in the forced swim test immobility and predictive value of a single assay in very old female mice

Abstract

The increase of prevalence of mental health problems in the elderly due to the aging of the population becomes an outstanding issue since in most individuals it happens in an already complex multimorbid scenario that may include frailty and age-related medical conditions. Depression, soon the major cause of global disease burden, can be found as an age-related comorbidity and frailty, or as part of neurodegenerative diseases and where females are more vulnerable to it. Thought the multifactorial aetiology and heterogeneous nature of depression render it difficult to be modelled in animals, active behaviours elicited in the Forced Swimming Test (FST) are used to screen antidepressant treatments. However, interpretation of immobility remains controversial. The present work addressed this issue in very-old (21 months) female C57bl/6 × 129 mice, also with the concern that a '6 minutes × 2 days' protocol can result demanding for a very-old animal and confounding factors may also arise. Animals were behaviourally assessed for sensorimotor functions, emotionality and anxiety-like behaviours, novelty seeking, and immobility in a 2-days FST. The predictive value of the first day evidenced that one single assay as sufficient for the assessment of immobility, and that the repeated test did not increase the immobility response. Moreover, sensorimotor tasks, neophobia in the corner test and emotional behaviour in the dark-light box correlated with FST immobility, contributing to the response. The results support the concern of geroscience on the relevance of using aged animals but also aware about taking into account the complexity of their comorbid scenario.

Keywords: Aging; Behaviour; Comorbidity; Corner-test; Dark-light box; Depression; Frailty; Geroscience; Hole-board; Methods; Open-field test; Porsolt; Sensorimotor functions; T-maze.