In addition to having a greater hypothermic response to 8-OHDPAT the singe-housed mice of Experiment 2 also, on average, had a lower starting temperature. Similar findings have been noted in other contexts. Singlehoused mice tend, for example, to prefer higher temperatures than their grouphoused conspecifics by approximately 1˚C and Spa¨ni and collaborators observed, similarly to the present study, that a cohort of single-housed male mice had significantly lower body temperatures than did their group-housed counterparts. The latter study furthermore concluded that the difference could not be explained through differing activity levels. The present study, and others studying core body temperatures in mice, have not found a trend between the number of group-housed mice to a cage and their body temperatures ; we can therefore speculate that huddling did not have an influence on the temperatures. Mice huddle together to minimize energy expenditure in their inactive period, but at the studied temperature and with the nest-building materials provided this huddling is probably used to lower the metabolic rate rather than to maintain body temperature. With this in mind, we tentatively suggest that the effect on the serotonergic system brought on by single housing not only affects the hypothermic response in the 8-OH-DPAT challenge, but may also influence core body temperature. Temperature dysregulation is not uncommon with depressions and is a known side effect with drugs targeting the serotonergic system, e.g. selective serotonin reuptake inhibitor drugs. Antidepressant compounds are extensively screened in mice in drug development, where differential 5-HT receptor expressions or activities may have profound SCH772984 consequences. It has for example been shown that the antidepressant effect of the SSRI fluoxetine in male C57BL/6 mice is modulated by the animals’ housing conditions. In fact, there are findings dating back more than four decades testifying to the fact that single housing may modulate the effect of neuroactive compounds. Inadvertently inducing depressive states in a subset of laboratory mice is of course a welfare concern, but it moreover influences experimental results. With a currently poor translational success rate for development of neuroleptics from animal studies to effect in humans, refining/controlling housing and husbandry conditions for the tested laboratory mice is essential. When evaluating and improving ambient conditions we propose that the 8-OH-DPAT challenge may serve as a simple, but powerful, tool in assessing the serotonergic states of laboratory mice. In closing, it is clear that male mice will not only choose social contact when given the option, but will also, when it is deprived, be negatively affected by its absence. The present study further suggests that the 8-OH-DPAT challenge may be a useful tool for assessing the effect of this social deprivation on the serotonergic state of male laboratory mice. Whereas the method requires, and merits, additional study, it potentially allows not only for an unbiased, biochemical evaluation of sub-acute stressors, but potentially allows for determining whether these detrimental effects can be counteracted. Those aged over 65 are the largest consumers of healthcare, and the recipients of the majority of prescribed medication. It is not surprising therefore that older people suffer more adverse drug reactions than younger adults, and are 7 times more likely to require hospitalisation due to an ADR.
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