Social Isolation Stress in Adolescence, but not Adulthood, Produces Hypersocial Behavior in Adult Male and Female C57BL/6J Mice

Abstract

Chronic stress during the developmental period of adolescence increases susceptibility to many neuropsychiatric diseases in adulthood, including anxiety, affective, and alcohol/substance use disorders. Preclinical rodent models of adolescent stress have produced varying results that are species, strain, sex, and laboratory-dependent. However, adolescent social isolation is a potent stressor in humans that has been reliably modeled in male rats, increasing adult anxiety-like and alcohol drinking behaviors, among others. In this study, we examined the generalizability and sex-dependence of this model in C57BL/6J mice, the most commonly used rodent strain in neuroscience research. We also performed a parallel study using social isolation in adulthood to understand the impact of adult social isolation on basal behavioral phenotypes. We found that 6 weeks of social isolation with minimal handling in adolescence through early adulthood [postnatal day (PD) 28-70] produced a hypersocial phenotype in both male and female mice and an anxiolytic phenotype in the elevated plus-maze in female mice. However, it had no effects in other assays for avoidance behavior or on fear conditioning, alcohol drinking, reward or aversion sensitivity, or novel object exploration in either sex. In contrast, 6 weeks of social isolation in adulthood beginning at PD77 produced an anxiogenic phenotype in the light/dark box but had no effects on any other assays. Altogether, our results suggest that: (1) adolescence is a critical period for social stress in C57BL/6J mice, producing aberrant social behavior in a sex-independent manner; and (2) chronic individual housing in adulthood does not alter basal behavioral phenotypes that may confound interpretation of behavior following other laboratory manipulations.

Animal Models of Depression: What Can They Teach Us about the Human Disease?

“…These effects are irreversible by resocialization [ 236 ], as observed in males but not in females [ 237 , 238 ]. SI reared rodents demonstrated despair-like behavior expressed as increased immobility time in the FST [ 76 , 239 ] that was reversed by chronic fluoxetine treatment [ 82 ], indicating a good predictive validity. SI-reared rats exhibited apathy-like behavior expressed as diminished grooming time and frequency in the splash test [ 75 ], mainly in males.…”

“…SI-reared rats exhibited apathy-like behavior expressed as diminished grooming time and frequency in the splash test [ 75 ], mainly in males. In addition, some studies showed that SI-reared rats, either male or female, demonstrated increased adult social interaction [ 77 , 82 , 240 ].…”

Friend of the Devil: Negative Social Influences Driving Substance Use Disorders

“…One recent study found that aSI in C57BL/6J mice resulted in a hypersocial phenotype in males and females and an anxiolytic phenotype in females. Alcohol consumption was not affected in either of the sexes (Rivera-Irizarry et al, 2020 ).…”

Establishment of a social conditioned place preference paradigm for the study of social reward in female mice

“…Reported results show that rewarding effects of social contact could be robustly observed in juvenile animals; however, the effect of social interaction is diminished or absent in early adulthood at the age of 8 weeks in male mice and at 11 weeks in females (Nardou et al, 2019). These results could be considered unexpected, as a lack of sCPP in adult mice would be at odds with other indices of social interaction preference in adult mice, such as the anxiogenic effects of isolation (Rivera-Irizarry et al, 2020) or communal nesting female behavior (Hayes, 2000).…”