Impact of social isolation on the oxytocinergic system: A systematic review and meta-analysis of rodent data.

Social isolation (SI) stress results from a combination of intrinsic and environmental factors and is associated with a variety of negative developmental outcomes. Oxytocin (OXT) might play a role in the consequences of SI in the brain and periphery. We conducted a systematic review and meta-analysis to compile data about the effects of SI in the oxytocinergic system of rats and mice, and its relation to behavioral alterations. Five databases (EMBASE, PsychNet, PubMed, Scopus, and Web of Science) were searched in March 2021, using ("Social Isolation" AND (mouse OR rat) AND (oxytocin OR oxytocin receptor)). This review followed the PRISMA guidelines, including registration in PROSPERO, and risk of bias assessment. The twelve articles included in this review indicated that SI was associated with decreased OXTR levels, resulting in behavioral alterations like increased aggression and anxiety-like behavior, hyperactivity, and diminished social behaviors and memory. No significant effects on OXT levels were observed. Administration of synthetic OXT or its agonists partially decreases those unwanted behaviors to similar levels of control animals.

Vulnerable and resilient cognitive performance related to early life stress: The potential mediating role of dopaminergic receptors in the medial prefrontal cortex of adult mice.

RATIONALE: Exposure to early life stress (ELS) is known to have pronounced effects on the prefrontal cortex (PFC). However, not all individuals exposed to ELS manifest the same neurobiological and cognitive phenotypes when adults. Dopamine signaling could be a key factor in understanding the effects of stress on PFC-related cognitive function. OBJECTIVES: We aimed to investigate the differential effects of ELS on cognitive performance of adult mice and the dopaminergic receptors expression in the PFC. METHODS: BALB/c males were exposed to the maternal separation (MS) procedure and their cognitive performance on the eight-arm radial maze (8-RAM) were assessed during adulthood. For molecular-level assessments, we performed mRNA expression analyses for dopamine receptors-DRD1, DRD2, DRD3-and Hers1 expression in the medial PFC. RESULTS: While MS produced an overall impairment on 8-RAM, the stressed animals could be divided in two groups based on their performance: those with impaired cognitive performance (vulnerable to maternal separation, V-MS) and those without any impairment (resilient to maternal separation, R-MS). V-MS animals showed increased DRD1 and DRD2 expression in comparison with other groups. Errors on 8-RAM were also positively correlated with DRD1 and DRD2 mRNA expression. CONCLUSIONS: Our findings suggest a potential role of the dopaminergic system in the programming mechanisms of cognitive vulnerability and resilience related to ELS.