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bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

39185229
10.1101/2024.08.12.607663
preprint
2
Article
Male and female mice respectively form stronger social aversive memories with same and different sex conspecifics
Beaver Jasmin N. http://orcid.org/0000-0002-4415-2861

Nicodemus Marissa M. http://orcid.org/0009-0003-5016-7896

Spalding Isabella R.
Dutta Sohini
Jasnow Aaron M. http://orcid.org/0000-0002-4015-4202

Gilman T. Lee http://orcid.org/0000-0001-8398-0195

10 9 2024
2024.08.12.607663https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.12.607663
nihpp-2024.08.12.607663.pdf
Abstract

Mice offer a wealth of opportunities for investigating brain circuits regulating multiple behaviors, largely due to their genetic tractability. Social behaviors are of translational relevance, considering both mice and humans are highly social mammals, and disruptions in human social behavior are key symptoms of myriad neuropsychiatric disorders. Stresses related to social experiences are particularly influential in the severity and maintenance of neuropsychiatric disorders like anxiety disorders, and trauma and stressor-related disorders. Yet, induction and study of social stress in mice is disproportionately focused on males, influenced heavily by their natural territorial nature. Conspecific-elicited stress (i.e., defeat), while ethologically relevant, is quite variable and predominantly specific to males, making rigorous and sex-inclusive studies challenging. In pursuit of a controllable, consistent, high throughput, and sex-inclusive paradigm for eliciting social stress, we have discovered intriguing sex-specific social aversions that are dependent upon the sex of both experimental and conspecific mice. Specifically, we trained male and female F1 129S1/SvlmJ × C57BL/6J mice to associate (via classical conditioning) same or different sex C57BL/6J conspecifics with a mild, aversive stimulus. Upon subsequent testing for social interaction 24 h later, we found that males socially conditioned better to male conspecifics by exhibiting reduced social interaction, whereas females socially conditioned better to male conspecifics. Serum corticosterone levels inversely corresponded to social avoidance after different sex, but not same sex, conditioning, suggesting corticosterone-mediated arousal could influence cross sex interactions. While our paradigm has further optimization ahead, these current findings reveal why past pursuits to develop same sex female social stress paradigms may have met with limited success. Future research should expand investigation of utilizing male mouse conspecifics to instigate social stress across sexes.
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pmc
