Social play exclusion model in adolescent rats: Monitoring locomotor and emotional behavior associated with social play and examining c-Fos expression in the brain.

The exclusion of social play within an adolescent group interferes with learning and the acquisition of essential social behavior during development and can cause modulations in the social brain areas. However, despite the importance of social play in adolescence, an in-depth explanation of its physiological mechanisms is limited because of the lack of experimental animal models that embody social play exclusion in human society. To determine the mechanism of social play in adolescence, we identified differences in emotional behavior and brain activity in animal models of social play exclusion that mimicked human society. Emotional changes in the social play exclusion and non-exclusion groups were examined by tracking social play-related social interaction behavior, social play-related space preference, social play-related locomotor behavior, and anxiety-like behavior using a behavioral data analysis program. Differences in brain activity among groups were identified using immunohistochemical staining. During the social play exclusion model, the rats preferred the partition zone to the other areas in the test chamber. The exclusion group preferred the partition and the center zone over the non-exclusion group. When comparing before and after the social play exclusion, the exclusion group showed a decrease in mobility and an increase in anxiety-like behavior compared to the non-exclusion group. We found that c-Fos expression in the dentate gyrus (DG) of the exclusion group was lower than that in the non-exclusion group, whereas c-Fos expression in the lateral habenula (LHb) of the exclusion group was higher than that in the non-exclusion group. Taken together, in adolescence, exclusion from social play with peers can increase anxiety-like behavior in the exclusion group and change the neuronal activity of the DG and LHb, suggesting that exclusion from social play is linked to modifications in the DG and LHb, which are regions associated with mood regulation.

Oxytocin modulation in the medial prefrontal cortex of pair-exposed rats during fear conditioning.

INTRODUCTION: Social buffering is the phenomenon, in which stress and fear reactions caused by exposure to stressful stimuli when animals are exposed to homogeneous relationships are attenuated. Social buffering reduces fear memory behavior such as escape, avoidance, and freezing behavior in rodents due to social existence. Here, we aimed to determine alterations of fear behavior and neural activity in the medial prefrontal cortex (mPFC) in response to the presence of another rat in fear-exposed conditions and to confirm the role of oxytocin in mPFC in regulating social buffering. METHODS: We performed a passive avoidance test and determined positive c-Fos expression in single- and pair-exposed rats. Anisomycin (a protein synthesis inhibitor) and oxytocin receptor regulators (carbetocin; agonist and atosiban; antagonist) were microinjected into the mPFC to clarify the role of oxytocin in the mPFC. RESULTS: While single-exposed rats showed a significant increase in both freezing and passive avoidance behaviors compared to control rats, pair-exposed rats showed significantly less fear behavior compared to single-exposed rats. The c-Fos expression in the prelimbic (PL) mPFC was significantly increased in pair-exposed rats compared to that in control and single-exposed rats. The pair-exposed effect was blocked by anisomycin injections into the PL mPFC of pair-exposed rats. Furthermore, when a carbetocin was injected into the PL mPFC in single-exposed rats, fear behavior was decreased, and these changes were blocked by atosiban. DISCUSSION: Our findings suggest that reduction of fear-related behavior induced by acute pair-exposure is mediated by oxytocin receptors in the PL mPFC. Pair exposure with conspecifics during fear-inducing situations helps coping with fear by significantly increasing the role of oxytocin in the PL mPFC.