Outcomes of early social experiences on glucocorticoid and endocannabinoid systems in the prefrontal cortex of male and female adolescent rats

Abstract

Social and emotional experiences differently shape individual’s neurodevelopment inducing substantial changes in neurobiological substrates and behavior, particularly when they occur early in life. In this scenario, the present study was aimed at (i) investigating the impact of early social environments on emotional reactivity of adolescent male and female rats and (ii) uncovering the underlying molecular features, focusing on the cortical endocannabinoid (eCB) and glucocorticoid systems. To this aim, we applied a protocol of environmental manipulation based on early postnatal socially enriched or impoverished conditions. Social enrichment was realized through communal nesting (CN). Conversely, an early social isolation (ESI) protocol was applied (post-natal days 14–21) to mimic an adverse early social environment. The two forms of social manipulation resulted in specific behavioral and molecular outcomes in both male and female rat offspring. Despite the combination of CN and ESI did not affect emotional reactivity in both sexes, the molecular results reveal that the preventive exposure to CN differently altered mRNA and protein expression of the main components of the glucocorticoid and eCB systems in male and female rats. In particular, adolescent females exposed to the combination of CN and ESI showed increased corticosterone levels, unaltered genomic glucocorticoid receptor, reduced cannabinoid receptor type-1 and fatty acid amide hydrolase protein levels, suggesting that the CN condition evokes different reorganization of these systems in males and females.

Communal nesting shapes the sex-dependent glutamatergic response to early life stress in the rat prefrontal cortex

“…Thus, the possibility exists that the CN condition shapes a distinct maturational trajectory of cortical excitatory synaptic inputs that undergo important remodeling during adolescence and are required for social play ( 46 ), in a sex-dependent manner. Importantly, as reported previously ( 35 ), pups reared in the CN condition emitted a lower number of USV when isolated from the nest at PND9, whereas no changes were observed in females, confirming the existence of sex-dependent differences in emotionality since the very first phases of life. Interestingly, these behavioral data are the first indication that male pups reared in a socially enriched environment (i.e., CN), known to represent a naturalistic setting able to induce stress resilience ( 25 ), might better cope to subsequent challenging events, as suggested by their reduced USV at PND9 and increased pinning during adolescence ( 47 , 48 ).…”

“…Mother-offspring interactions have been evaluated as previously described ( 33 , 34 ). CN reduced maternal behavior and ultrasonic vocalizations (USV) of only male pups at PND9 (data not shown), similarly to the data obtained in our previous study ( 35 ). On PND21, pups were weaned and housed in groups belonging to the same environmental condition.…”

Effects of unburned tobacco smoke on inflammatory and oxidative mediators in the rat prefrontal cortex

“…At the end of the experimental protocol, animals were sacrificed by decapitation. For each rat, the PFC was collected, as previously reported ( Rullo et al, 2023 ) and according to the Rat Brain Atlas ( Paxinos and Watson, 2013 ). Tissues were immediately stored at −80°C for further ex vivo analysis.…”