Head movement: a novel serotonin-sensitive behavioral endpoint for tail suspension test analysis

Abstract

The tail suspension test (TST) as an antidepressant and depression-related behavior screen, has many advantages over the forced swim test (FST) in terms of procedural simplicity and consistent SSRI response. However, the FST has traditionally offered more specific neuromodulatory information by differentiating between serotonin (5-HT) and norepinephrine sensitive behavior categories. Head movement is a newly characterized behavior endpoint in the FST and TST with a selective 5-HT sensitivity. In this investigation, we show that the baseline and drug response profile of head movement previously found in the 129S6 strain of mice (Lockridge et al., 2010) is reproducible in the C57 strain. Head movement is inversely correlated to FST swimming and elevated in the TST by SSRI administration. The use of a weighted bin sample analysis method differentiates TST behaviors into fluoxetine-responsive head movement and desipramine-responsive struggling. The use of 5-HT subtype receptor agonists, after depleting endogenous 5-HT with pCPA, shows the head movement suppressing effect of 5-HT2A and 5-HT2C postsynaptic receptor activation. 5-HT1A and 5-HT1B agonists were ineffective. We propose that a head movement focused analysis can add sensitive and reliable 5-HT detection capability to mouse TST testing with minimal effort but significant reward.