Individual Differences in Volitional Social Self-Administration and Motivation in Male and Female Mice Following Social Stress

• Published in: Biological psychiatry (1969) 2024-08, Vol.96 (4), p.309-321
• Main Authors: Navarrete, Jovana, Schneider, Kevin N., Smith, Briana M., Goodwin, Nastacia L., Zhang, Yizhe Y., Salazar, Axelle S., Gonzalez, Yahir E., Anumolu, Pranav, Gross, Ethan, Tsai, Valerie S., Heshmati, Mitra, Golden, Sam A.
• Format: Article
• Language: English
• Subjects: Reward; Self-administration; Sex differences; Social; Stress
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2024.01.007

A key challenge in developing treatments for neuropsychiatric illness is the disconnect between preclinical models and the complexity of human social behavior. We integrate voluntary social self-administration into a rodent model of social stress as a platform for the identification of fundamental brain and behavior mechanisms underlying stress-induced individual differences in social motivation. Here, we introduced an operant social stress procedure in male and female mice composed of 3 phases: 1) social self-administration training, 2) social stress exposure concurrent with reinforced self-administration testing, and 3) poststress operant testing under nonreinforced and reinforced conditions. We used social-defeat and witness-defeat stress in male and female mice. Social defeat attenuated social reward seeking in males but not females, whereas witness defeat had no effect in males but promoted seeking behavior in females. We resolved social stress-induced changes to social motivation by aggregating z-scored operant metrics into a cumulative social index score to describe the spectrum of individual differences exhibited during operant social stress. Clustering does not adequately describe the relative distributions of social motivation following stress and is better described as a nonbinary behavioral distribution defined by the social index score, capturing a dynamic range of stress-related alterations in social motivation inclusive of sex as a biological variable. We demonstrated that operant social stress can detect stable individual differences in stress-induced changes to social motivation. The inclusion of volitional behavior in social procedures may enhance the understanding of behavioral adaptations that promote stress resiliency and their mechanisms under more naturalistic conditions.