Sex Differences in the Enduring Effects of Social Deprivation during Adolescence in Rats: Implications for Psychiatric Disorders

The exposure to adverse environmental situations during sensitive periods of development may induce re-organizational effects on different systems and increase the vulnerability to develop psychiatric disorders later in life. The adolescent period has been demonstrated extremely susceptible to stressful events. However, most of the studies focused on the immediate effects of stress exposure and few of them investigated sex differences. This raised the question if these modulations might also be long-lasting and how the differential maturational events taking place during adolescence between males and females might have a role in the detrimental effects of stress. Given the importance of social play for the right maturation of behavior during adolescence, we used the preclinical model of social deprivation, based on the lack of all social contacts, for four weeks after weaning, followed by re-socialization until adulthood. We found that both male and female animals reared in isolation during adolescence developed an anhedonic phenotype at adulthood, without any impairments in the cognitive domain. At molecular level, these functional changes were associated with sex-specific impairments in the expression of neuroplastic markers as well as of hypothalamic-pituitary-adrenal axis-related genes. Lastly, we also reported anatomically-selective changes associated with the enduring effects of social isolation.