Establishment of a social conditioned place preference paradigm for the study of social reward in female mice

Abstract

Social interactions can be and often are rewarding. The effect of social contact strongly depends on circumstances, and the reward may be driven by varied motivational processes, ranging from parental or affiliative behaviors to investigation or aggression. Reward associated with nonreproductive interactions in rodents is measured using the social conditioned place preference (sCPP) paradigm, where a change in preference for an initially neutral context confirms reinforcing effects of social contact. Here, we revised the sCPP method and reexamined social reward in adult female mice. Contrary to earlier studies, we found that robust rewarding effects of social contact could be detected in adult (14-week-old) female C57BL/6 mice when the sCPP task was refined to remove confounding factors. Strikingly, the rewarding effects of social interaction were only observed among female siblings who remained together from birth. Contact with same-age nonsiblings was not rewarding even after 8 weeks of cohousing. Other factors critical for the social reward effect in the sCPP paradigm included the number of conditioning sessions and the inherent preference for contextual cues. Thus, we show that social interaction is rewarding in adult female mice, but this effect strictly depends on the familiarity of the interaction partners. Furthermore, by identifying confounding factors, we provide a model to study the mechanisms underlying the rewarding effects of nonreproductive social interaction in adult mice.

Prosocial behavior, social reward and affective state discrimination in adult male and female mice

“…The finding that sCPP can be elicited in adult mice using contact with age and sex matched conspecifics as a reward appears contradictory to the previous findings by Nardou and collaborators in 2019, who have shown that sCPP was no longer observed at the age of 8 weeks in male, and at 11 weeks in female mice 35 . However, in the study the short (2 days) conditioning protocol was used 35 , and we have recently shown that sCPP can be observed in adult (>11 weeks) female mice, when the longer, 6-day, conditioning protocol is used 34 . Here, to assess if the effect of conditioning length is similar in males, we performed additional experiment on male mice using a 2-day conditioning protocol ( Fig.2D-E, Table S5-S6 ).…”

“…Two sets of conditioning contexts were used ( Table S13 ), and the results from both contexts were pooled. When the number of animals conditioned on different bedding types were not equal, the number of animals for each type of bedding was equalized by randomly removing the appropriate number of cases from the larger group using an R script as described in 34 .…”

“…sCPP was performed as previously described 34,43 . The procedure consisted of three phases: pretest, conditioning phase, and posttest.…”

“…To assess prosocial behavior, we have developed a food-motivated prosocial choice task based on the rat task described by Hernandez-Lallement and collaborators 11 , with a custom-designed apparatus and schedule adapted for mice. Empathy was tested in a paradigm modified from Scheggia et al in 2020, where sensitivity to the emotional state of interaction partners was assayed 23 and social reward was tested in the social conditioned place preference task 34 . We found that, similar to the case in humans, sex had a significant effect on the propensity for prosocial choices; however, females and males did not differ with respect to levels of social reward and empathy.…”