Social deficits induced by peripubertal stress in rats are reversed by resveratrol

Abstract

a b s t r a c tAdolescence is increasingly recognized as a critical period for the development of the social system, through the maturation of social competences and of their underlying neural circuitries. The present study sought to test the utility of resveratrol, a dietary phenol recently reported to have mood lifting properties, in modulating social interaction that is deficient following early life adversity. The main aims were to 1) pharmacologically restore normative social investigation levels dampened by peripubertal stress in rats and 2) identify neural pathways engaged by this pharmacological approach. Following peripubertal (P28e42) stress consisting of unpredictable exposures to fearful experiences, at adulthood the subjects' propensity for social exploration was examined in the three-chamber apparatus, comparing time invested in social or non-social investigation. Administered intraperitoneally 30 min before testing, resveratrol (20 mg/kg) normalized the peripubertal stress-induced social investigation deficit seen in the vehicle group, selectively altering juvenile but not object exploration. Examination of prefrontal cortex subregion protein samples following acute resveratrol treatment in a separate cohort revealed that while monoamine oxidase A (MAOA) enzymatic activity remained unaltered, nuclear AKT activation was selectively increased in the infralimbic cortex, but not in the prelimbic or anterior cingulate cortex. In contrast, androgen receptor nuclear localization was increased in the prelimbic cortex, but not in the infralimbic or anterior cingulate cortex. This demonstration that social contact deficits are reversed by resveratrol administration emphasizes a prosocial role for this dietary phenol, and evokes the possibility of developing new treatments for social dysfunctions.

Peripubertal stress-induced heightened aggression: modulation of the glucocorticoid receptor in the central amygdala and normalization by mifepristone treatment

“…Peripubertal stress leads to higher GR expression in the CeA, along with reduced sociability and increased aggression First, we confirmed our previous findings [11,[36][37][38] indicating that peripubertal stress leads to reduced sociability and increased aggression when animals are tested at adulthood (Fig. 1a).…”

Stress Impacts the Regulation Neuropeptides in the Rat Hippocampus and Prefrontal Cortex

“…Male rats from different litters were distributed into different home cages in groups of two to three non‐siblings 21 d after birth (P21) and each cage was randomly assigned to control (CTRL, six animals) or peripubertal stress (PPS, six animals) conditions. At P28, animals underwent the well‐established peripubertal stress protocol previously developed in Professor Sandi's lab . PPS group was exposed to two fear‐inducing stressors: the synthetic fox odor trimethylthiazoline (Phero Tech, Delta, BC, Canada) administered in a plastic box (38 × 27.5 × 31 cm) and exposure to an elevated platform (12 × 12 cm) presented in a variable schedule in a span of 7 d across the P28–P42 period.…”

An energetic view of stress: Focus on mitochondria

“…For example, treatment with a ketogenic diet – a high-fat low-carbohydrate diet that enhances mitochondrial function – was able to ameliorate impaired mitochondrial respiration and deficits in social behaviors in a valproic acid model of autism in rats (Ahn et al, 2014). In another study, acute infusion in rodents of resveratrol, a compound that activates AMPK-induced mitochondrial biogenesis, counteracted diminished sociability induced by peripubertal stress (Poirier et al, 2014). Similarly, treatment with the antioxidant N-acetyl cysteine reversed impairment in social isolation and accumulated striatal ATP levels observed in a rat model of social isolation rearing stress in rats (Moller et al, 2013).…”