An Operant Social Self-administration and Choice Model in Mice

Little is known about how social factors contribute to neurobiology or neuropsychiatric disorders. The use of mice allows one to probe the neurobiological bases of social interaction, offering the genetic diversity and versatility to identify cell types and neural circuits of social behavior. However, mice typically show lower social motivation compared with rats, leading to the question of whether mice should be used to model complex social behaviors displayed by humans. Studies on mouse social behavior often rely on measures such as time spent in contact with a social partner or preference for a social-paired context, but fail to assess volitional (subject-controlled) rewarding social interaction. Here, we describe a volitional social self-administration and choice model that is an extension of our previous work on rats. Using mice, we systematically compared female adolescent and adult C57BL/6 mice and outbred CD1 mice, showing that operant social self-administration, social seeking during periods of isolation and choice of social interaction over palatable food is significantly stronger in female CD1 mice than in female C57BL/6J mice, independently of age. We describe the requirements for building the social self-administration and choice apparatus and we provide guidance for studying the role of operant social reward in mice. We also discuss its use to study brain mechanisms of operant social reward, potentially extending its application to mouse models of neuropsychiatric disorders. The training commonly requires ~4 weeks for stable social self-administration and 3-4 additional weeks for tests, including social seeking and choice.