Abstract
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.
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Data availability
The main data discussed in this protocol are available in the supporting primary research paper (https://doi.org/10.1016/j.biopsych.2021.10.023)
Code availability
The Med-Associates programs are available upon request of the corresponding authors (L.A.R. and M.V.). Files necessary for 3D printing the partner chamber are provided in the Supplementary Software.
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Acknowledgements
We thank E. Hart for his help with 3D printing. We thank F. Vautier and the NIDA Transgenic Breeding Facility for assistance in breeding the FosGFP × CD1 hybrid mice. We thank Drs. Y. Shaham and B. Hope for input and support in developing the model. The research was supported by the NIDA Intramural Research Program (L.A.R.), a grant from NIDA (DA047976) (M.V.) and a BBRF Young Investigator Grant Award (28897; M.V.).
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L.A.R., F.M.H., S.S.L. and M.V. contributed to various aspects of the study, including the design and performance of the research and the writing of the paper.
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Nature Protocols thanks Loren Martin and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.
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Key references using this protocol
Ramsey, L. A. et al. Biol. Psychiatry 91, 988–997 (2022): https://doi.org/10.1016/j.biopsych.2021.10.023
Venniro, M. & Shaham, Y. Nat. Prot. 15, 1542–1559 (2020): https://doi.org/10.1038/s41596-020-0296-6
This protocol is an extension to: Nat. Protoc. 15, 1542–1559 (2020): https://doi.org/10.1038/s41596-020-0296-6
Supplementary information
Supplementary Software 1
Design file template for partner chamber (Partner chamber.stl). 2. Design file template for partner door (Partner door.stl). 3. Design file template for bedding box (bedding box partner chamber.stl). 4. Design file template for bedding box [modifiable] (bedding box partner chamber.gcode). 5. Design file template for partner chamber door [modifiable] (Door partner chamber 1 box.form). 6. Design file template for Partner chamber door [modifiable] (Door partner chamber 3 box.form).
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Ramsey, L.A., Holloman, F.M., Lee, S.S. et al. An operant social self-administration and choice model in mice. Nat Protoc 18, 1669–1686 (2023). https://doi.org/10.1038/s41596-023-00813-y
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DOI: https://doi.org/10.1038/s41596-023-00813-y
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