Adverse Social Experiences in Adolescent Rats Result in Enduring Effects on Social Competence, Pain Sensitivity and Endocannabinoid Signaling

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.

Disruption of behavior and brain metabolism in artificially reared rats

“…Artificial rearing allows controlling tactile sensory inputs and provides a constant composition of milk to the pup. Lack of tactile sensory input has a clear relationship with our findings on the somatosensory cortex and previous results in the peripheral nervous system (Segura et al, ; Sieben et al, ; Schneider et al, ). The constancy in milk composition is, however, a main constrain.…”

Effects of neonatal handling on play and anxiety in F344 and Lewis rats

“…rats. This suggests that F344 rats may be particularly unresponsive to the contagious nature of play and is consistent with what has been reported by others when F344 rats are housed with rats of a more playful strain during adolescence (Schneider, Bindila et al, 2016;Schneider, Pätz, Spanagel, & Schneider, 2016). If so, then the apparent inability of neonatal handling to impact nape contacts in F344 rats may have less to do with how rats of this strain respond to neonatal handling and more to do with an inability to adjust their behavior in response to the ebb and flow of a play bout.…”

“…in the developing organism since removing the opportunity to play in young rats can have a number of adverse consequences on later behavior and social/emotional functioning (Pellis & Pellis, 2007;Spinka, Newberry, & Bekoff, 2001; Van den Berg et al, 1999) as well as cognitive functioning (Baarendse, Counotte, O'Donnell, & Vanderschuren, 2013). Housing juvenile rats with non-playful partners after weaning leads to the same constellation of social and cognitive deficits (Burleson et al, 2016;Pellis, Williams, & Pellis, 2017;Schneider, Bindila et al, 2016) further supporting the idea that these deficits are due to a lack of play rather than a lack of social contact per se. All of this would suggest that the young mammalian brain is programmed and motivated to engage in playful behaviors, with adverse consequences resulting when opportunities for play are prevented.…”

Computational Psychiatry in Borderline Personality Disorder

“…In people, social rejection leads to alterations in subsequent social behavior [10] [11] and decreased pain sensitivity [12]. In rodents, adolescent social rejection produces effects on behavior and pain tolerance that mirror the results in human subjects [13]. An innovative paradigm also examined trust in the same rodents: animals were offered a novel food that they could smell on another rat's whiskers.…”