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Sex differences in appetitive and reactive aggression

Abstract

Aggression is an evolutionarily conserved, adaptive component of social behavior. Studies in male mice illustrate that aggression is influenced by numerous factors including the degree to which an individual finds aggression rewarding and will work for access to attack and subordinate mice. While such studies have expanded our understanding of the molecular and circuit mechanisms of male aggression very little is known about female aggression, within these established contexts. Here we use an ethologically relevant model of male vs. female aggression by pair housing adult male and female outbred CFW mice with opposite sex cage mates. We assess reactive (defensive) aggression in the resident intruder (RI) test and appetitive (rewarding) aggression in the aggression conditioned place preference (CPP) and operant self-administration (SA) tests. Our results show dramatic sex differences in both qualitative and quantitative aspects of reactive vs. appetitive aggression. Males exhibit more wrestling and less investigative behavior during RI, find aggression rewarding, and will work for access to a subordinate to attack. Females exhibit more bites, alternate between aggressive behaviors and investigative behaviors more readily during RI, however, they do not find aggression to be rewarding or reinforcing. These results establish sex differences in aggression in mice, providing an important resource for the field to better understand the circuit and molecular mechanisms of aggression in both sexes.

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Fig. 1: Male and Female CFW mice engage in similar amounts of aggressive and investigative social behavior.
Fig. 2: Male and female mice display distinct investigative and aggressive behaviors.
Fig. 3: Hidden Markov model of social behavior in the resident intruder paradigm.
Fig. 4: Males and females are similar in reactive but not appetitive aggression.

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Funding

The research was supported R01MH127820 (SJR), R01MH114882 (SJR), R01MH104559 (SJR), R01MH120514 (SJR), R01MH120637 (SJR), R00DA045662 (SAG), P30DA048736 (SAG), NARSAD Young Investigator Award 27082 (SAG), and F31MH125587-01 (NLG). Some figures created with BioRender.com.

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AVA, CJB, NLG, SAG & SJR designed experiments. AVA, CJB, NLG, LL, JN, YZ, VT, & RDC performed experiments. AVA, CJB, & NLG analyzed data. AVA, CJB, NLG, SAG & SJR wrote and edited the manuscript.

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Correspondence to Sam A. Golden or Scott J. Russo.

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Aubry, A.V., Joseph Burnett, C., Goodwin, N.L. et al. Sex differences in appetitive and reactive aggression. Neuropsychopharmacol. 47, 1746–1754 (2022). https://doi.org/10.1038/s41386-022-01375-5

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