A proposal for refining the forced swim test in Swiss mice

Abstract

The forced swim test (FST) is a preclinical test to the screening of antidepressants based on rats or mice behaviours, which is also sensitive to stimulants of motor activity. This work standardised and validated a method to register the active and passive behaviours of Swiss mice during the FST in order to strength the specificity of the test. Adult male Swiss mice were subjected to the FST for 6 min without any treatment or after intraperitoneal injection of saline (0.1 ml/10 g), antidepressants (imipramine, desipramine, or fluoxetine, 30 mg/kg) or stimulants (caffeine, 30 mg/kg or apomorphine, 10mg/kg). The latency, frequency and duration of behaviours (immobility, swimming, and climbing) were scored and summarised in bins of 6, 4, 2 or 1 min. Parameters were first analysed using Principal Components Analysis generating components putatively related to antidepressant (first and second) or to stimulant effects (third). Antidepressants and stimulants affected similarly the parameters grouped into all components. Effects of stimulants on climbing were better distinguished of antidepressants when analysed during the last 4 min of the FST. Surprisingly, the effects of antidepressants on immobility were better distinguished from saline when parameters were scored in the first 2 min. The method proposed here is able to distinguish antidepressants from stimulants of motor activity using Swiss mice in the FST. This refinement should reduce the number of mice used in preclinical evaluation of antidepressants.

Keywords: ANOVA; Analysis of Variance; Animal model; Antidepressants; C57Bl6/J; CD-1; CEUA; EV; Eingenvectors; Ethics Committee on Animal Use; FST; Forced Swimming Test; Inbred Strain of mice from The Jackson Laboratory; MANOVA; Methodological refinement; Multivariate Analysis of Variance; NMRI; NSRIs; Norepinephrine Selective Reuptake Inhibitors; Outbred Strain of mice from Charles River Laboratory; Outbred strain of mice from Charles River Laboratory; PCA; Preclinical studies; Principal Component Analysis; Psychopharmacology; S.E.M.; SSRIs; Selective Serotonin Reuptake Inhibitors; Standard Error of the Mean; Stimulants.