Persistence of behaviours in the Forced Swim Test in 3xTg-AD mice at advanced stages of disease

Abstract

Forced Swimming Test (FST) models behavioural despair in animals by loss of motivation to respond or the refusal to escape. The present study characterizes the behavioural responses of 12-month-old male 3xTg-AD mice in FST as compared to age-matched no-transgenic (NTg) mice. Paradoxical results were consistently found from what would be expected from their BPSD (Behavioural and Psychological Symptoms of Dementia)-like profile. The comprehensive analysis of the ethogram shown in the FST considered the intervals of the test (0-2 and 2-6min), all the elicited behavioural responses (immobility, swimming and climbing) and their features (total duration, frequency of episodes and mean duration). Both genotypes showed equal number of swimming episodes and climbing attempts during the first interval, that resulted in high swimming times, short climbing and scarce immobility. Thereafter, the NTg mice showed a behavioural shift over time and the immobility response showed up. In contrast, all the measures consistently evidenced that 3xTg-AD persisted with the previous behavioural pattern. Genotype differences consisted in less number of episodes of immobility and swimming, and a low immobility time in favour of swimming. No differences were found in 'climbing' attempts. The behavioural response observed is discussed as a lack of ability of 3xTg-AD mice to shift behaviour over time that may result of poorest cognitive flexibility and copying with stress strategies more than behavioural despair per se.

Keywords: 3xTg-AD mice; Alzheimer's disease; Behavioural despair; Cognitive-flexibility; Copying with stress; Forced Swimming Test.