Social affective behaviors among female rats involve the basolateral amygdala and insular cortex

Abstract

The ability to detect, appraise, and respond to another's emotional state is essential to social affective behavior. This is mediated by a network of brain regions responsible for integrating external cues with internal states to orchestrate situationally appropriate behavioral responses. The basolateral amygdala (BLA) and the insular cortex are reciprocally connected regions involved in social cognition and prior work in male rats revealed their contributions to social affective behavior. We investigated the functional role of these regions in female rats in a social affective preference (SAP) test in which experimental rats approach stressed juvenile but avoid stressed adult conspecifics. In separate experiments, the BLA or the insula were inhibited by local infusion of muscimol (100ng/side in 0.5μL saline) or vehicle prior to SAP tests. In both regions, muscimol interfered with preference for the stressed juvenile and naive adult, indicating that these regions are necessary for appropriate social affective behavior. In male rats, SAP behavior requires insular oxytocin but there are noteworthy sex differences in the oxytocin receptor distribution in rats. Oxytocin (500nM) administered to the insula did not alter social behavior but oxytocin infusions to the BLA increased social interaction. In sum, female rats appear to use the same BLA and insula regions for social affective behavior but sex differences exist in contribution of oxytocin in the insula.

Serotonin modulates social responses to stressed conspecifics via insular 5-HT2Creceptors in rat

“…Importantly there are noteworthy sex differences in the prevalence of these disorders, sex differences in rodent social behavior (Dumais & Veenema, 2016) and sex-specific effects of CRF and OT in the insula of the SAP test (Djerdjaj et al, 2023; Rieger, Varela, et al, 2022; Rogers-Carter, Varela, et al, 2018). Although prior reports note some sex differences in 5-HT immunoreactivity and neurochemistry (Carlsson & Carlsson, 1988), we did not find any evidence of sex differences in our behavioral, pharmacological or mRNA colocalization experiments.…”

“…The SAP tests allow for the quantification of social interactions initiated by a test rat toward either a stressed or unstressed conspecific, providing insight into the test animal’s discrimination of socioemotional affective cues; they were conducted exactly as previously described (Djerdjaj et al, 2022, 2023; Rieger, Varela, et al, 2022; Rieger, Worley, et al, 2022; Rogers-Carter, Djerdjaj, et al, 2018; Rogers-Carter et al, 2019; Rogers-Carter, Varela, et al, 2018). Briefly, the SAP test begins when a test rat is placed in the center of an arena containing chambers for conspecifics on opposite sides of the arena.…”

“…All animals were allowed to acclimate to the vivarium for a minimum of 7 days prior to any experimental or surgical procedures and given access to food and water ad libitum. Consistent with our recent experiments in female rats, on the 5 days preceding behavioral testing male and female rats were gently wrapped in a cloth towel for 1 minute to habituate the rats to experiment handling and reduce stress associated with injections (Djerdjaj et al, 2023;Rieger, Varela, et al, 2022). The vivarium maintained a 12 h light/dark cycle and all behavioral tests occurred within the first 4 h of the light cycle.…”

“…Neurobiological treatments that inhibit insular activity prevent both of these patterns (Djerdjaj et al, 2022(Djerdjaj et al, , 2023Rieger, Varela, et al, 2022;Rieger, Worley, et al, 2022;Rogers-Carter, Djerdjaj, et al, 2018;Rogers-Carter, Varela, et al, 2018). Because the insula contains direct input from the DRN (Gehrlach et al, 2020;Vertes, 1991;Vertes & Kocsis, 1994) and 5-HT2C receptors (Clemett et al, 2000;Linley et al, 2013), we hypothesized that 5-HT and 5-HTergic input to insular 5-HT 2C receptors may be necessary for social affective behaviors in the SAP test.…”