C57BL/6J mice fail to exhibit preference for social novelty in the three-chamber apparatus

Laboratory models of neurodevelopmental disorders may be useful in assessing investigation and preference for social partners in mice. One such mouse model, the three-chamber test, is increasingly used as an index of social preference. The first phase measures preference for a social stimulus over an identical chamber without a stimulus mouse. The second phase measures preference for a novel mouse compared to the familiar mouse when the latter is presented in the previously empty chamber. In this study we provided an additional analysis of the second phase of the three-chamber test procedure, reversing the typical placement of the novel and familiar stimulus animals. In the first study, male C57BL/6J mice subjects encountered C57BL/6J stimuli and preferred a novel mouse over an empty chamber but failed to show a preference for the novel mouse in Phase 2 when the stimuli presentation was reversed. In an additional study, male C57BL/6J subjects encountered outbred CD-1 mice as stimuli, showing no significant novelty preference in either phase. Specific behavioral indices of investigation were similar to these duration findings with no enhancement of investigation when the novel stimulus mouse was encountered in the chamber in which the initial social stimulus was presented. These data suggest that C57BL/6J mice may show enhanced investigation/preference of novel social stimuli in the three-chamber test only when these stimuli are presented in a relatively novel context.