Abstract
Social affiliation is essential for many species and gains significant importance during adolescence. Disturbances in social affiliation, in particular social rejection experiences during adolescence, affect an individual’s well-being and are involved in the emergence of psychiatric disorders. The underlying mechanisms are still unknown, partly because of a lack of valid animal models. By using a novel animal model for social peer-rejection, which compromises adolescent rats in their ability to appropriately engage in playful activities, here we report on persistent impairments in social behavior and dysregulations in the endocannabinoid (eCB) system. From postnatal day (pd) 21 to pd 50 adolescent female Wistar rats were either reared with same-strain partners (control) or within a group of Fischer 344 rats (inadequate social rearing, ISR), previously shown to serve as inadequate play partners for the Wistar strain. Adult ISR animals showed pronounced deficits in social interaction, social memory, processing of socially transmitted information, and decreased pain sensitivity. Molecular analysis revealed increased CB1 receptor (CB1R) protein levels and CP55, 940 stimulated [35S]GTPγS binding activity specifically in the amygdala and thalamus in previously peer-rejected rats. Along with these changes, increased levels of the eCB anandamide (AEA) and a corresponding decrease of its degrading enzyme fatty acid amide hydrolase (FAAH) were seen in the amygdala. Our data indicate lasting consequences in social behavior and pain sensitivity following peer-rejection in adolescent female rats. These behavioral impairments are accompanied by persistent alterations in CB1R signaling. Finally, we provide a novel translational approach to characterize neurobiological processes underlying social peer-rejection in adolescence.
Highlights
The need for stable social attachments represents a ubiquitous phenomenon within social groups
We refined our initial approach to model long-term peer-rejection in adolescent female Wistar rats
The present results demonstrate that the inability to adequately engage in playful peer-interaction during adolescence results in lasting impairments in pain sensitivity and a variety of social abilities in adulthood by decreasing social interaction behavior, social memory and the processing of socially transmitted information
Summary
The need for stable social attachments represents a ubiquitous phenomenon within social groups. Adolescence is crucial for the maturation of social skills, which are essential for successful social inclusion and reproduction and enable an individual to slowly separate from the protective influence of the family (Spear, 2000). This individuation from parents is accompanied by a deepening of relationships and intimacy with peers, especially among girls (Larson and Richards, 1991). The neurobiological mechanisms mediating the consequences of social rejection remain largely unknown At this point valid animal models represent a crucial link to increase our insight into mechanistic processes underlying social rejection and its consequences
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