Kalliokoski, O., Teilmann, A. C., Jacoben, K. R. et al. 2014. Do singly housed male mice get lonely? Evidence of depressive states after short-term single housing of BALB/c and C57BL/6 mice. American Association for Laboratory Animal Science [AALAS] Meeting Official Program, 597. (Abstract #P184).

Through behavioral and preference studies we know that mice prefer company. Laboratory mice should thus never be housed alone, if a viable option exists. Yet single housing is a fairly common practice, in particular with male mice, because an experimental protocol requires it or because groups exhibiting aggression need to be broken apart. But what are the negative consequences of single housing, if indeed there are any? Does the singly housed male mouse get lonely? Having found inconsistencies in results obtained from singly housed mice in welfare studies we hypothesized that single housing of male mice is capable of inducing depressive states. We also hypothesized that this is demonstrable through challenges with serotonin receptor agonists. The agonist 8-OH-DPAT induces a hypothermic response where the degree of hypothermia can be related to the density/activity of the target serotonin receptor 5-HT1A. The 5-HT1A activity is, in this paradigm, a well-consolidated proxy measure of depression. In a proof-of-concept study, mice were injected subcutaneously with 40 μg of the agonist and the core body temperatures were recorded before and 30 min after the injection. We were able to demonstrate that 3 wk of single housing was enough to induce a significantly exacerbated hypothermic response (F4,31 = 3.50, P = 0.015) in 11-wk-old BALB/c mice (n = 8) when compared with age-matched group housed controls (n = 8). By further screening a cohort of 215 male breeders on a C57BL/6 background - group housed and singly housed - selected at random from 2 breeding facilities, we were able to demonstrate that this effect was ubiquitous. Accounting for age, weight, substrain, and differences in baseline body temperatures, a singly housed C57BL/6 would present with a 0.5 °C (95% CI: 0.3 to 0.7 °C) attenuated hypothermic response for every 10 d of single housing when challenged with 8-OH-DPAT. Our findings indicate that even shorter durations of single housing of male mice may constitute a welfare concern meriting investigation. Furthermore, as antidepressant drug candidates are often first screened in mice, our results suggest that the housing conditions may be of utmost concern in order to obtain reliable results in these studies.