of age based on recent MRI work (Semple et al., 2013). Based on these estimates, the first days of weaning may correspond to the early childhood years. Notably, in rodent literature, the period from the first day of weaning to early adulthood is often referred to as adolescence (Lukkes et al., 2009). This period captures different developmental periods in rodents’ lives: puberty/preadolescence (postnatal day 21–28), early adolescence (pnd: 28–34), mid‐adolescence (pnd: 34–46) and early adulthood (pnd: 46–56; Lukkes et al., 2009). As such, the postweaning isolation studies aim to understand the extent to which the timing and duration of social isolation leads to lasting changes in rats’ biological systems as well as behavior.
The postweaning period reflects an important time for engaging in “social play” with litter mates and peers. Therefore, deprivation from opportunities to engage in “social play” is considered to be the main mechanism accounting for the effects of postweaning social isolation on rats’ behavior (Špinka et al., 2001). For example, although social isolation for the first 25 days after weaning led to heightened aggression and hyperarousal in novel environments, male rats that were allowed to have daily play bouts with a conspecific were protected from this effect (Einon et al., 1978; Potegal & Einon, 1989). Likewise, the effects of postweaning social isolation were not long‐lasting in species that do not typically engage in social play in adolescence (Lukkes et al., 2009). Thus, being deprived of social play may be a mechanism that can at least partially explain the effects of postweaning social isolation on rodents.
Postweaning social isolation was associated with both cognitive and emotional deficits. It was shown to lead to poor cognitive outcomes including impaired rule learning, recognition memory, and prepulse inhibition of acoustic startle (see Fone & Porkess, 2008), and resulted in reduced social interaction, increased aggression and antisociality, and anxiety‐like behaviors; though the effects depend on the timing and duration of the social isolation as well as the sex of the rodent (see Fone & Porkess, 2008). In both male and female rats, social isolation experienced from pre‐ to mid‐adolescence (about 15 days) led to increases in anxiety‐like behaviors including longer latency to emerge in an unfamiliar open‐field and reduced defensive burying reflecting lower levels of proactive coping (Arakawa, 2005, 2007). In males, the majority of these anxiety‐like behaviors did not disappear even after resocialization up to 90 days, suggesting that these behaviors are likely not reversible. Importantly, when male rats experienced the same duration of isolation in late adolescence, they did not show anxiety‐like behaviors. In contrast, in female rats, social isolation experienced in pre‐ to mid‐adolescence as well as experienced in adulthood led to anxiety‐like behaviors (Arakawa, 2007). These findings indicate that postweaning social isolation leads to poor developmental outcomes in both males and females. However, in females, these negative effects seem to be reversible by resocialization experiences, whereas, in males, certain developmental impairments may not be reversible by resocialization, suggesting that the adolescence period may constitute a critical period for the effects of social isolation in male rats.
Postweaning social isolation has been proposed to lead to anxiety‐like behaviors by disrupting the functioning of the neurotransmitter systems, specifically the serotonin and dopamine systems, which are known to modulate emotive behaviors and mental health systems (Lukkes et al., 2009). These systems follow a protracted course of development and are not fully developed until early to late adolescence. Postweaning social isolation has been shown to alter the functioning of these systems in a brain region‐specific manner. For example, it leads to increases in serotonergic activity in the medial prefrontal cortex, but decreases in in the hippocampus and decreases in the dopamine innervation in the medial prefrontal cortex but increases in dopaminergic activity in the NAc in male rats (see Lukkes et al., 2009). It is also possible that social isolation leads to deficits in behaviors by affecting the interactions between serotonin and dopamine functioning within the limbic system (Lukkes et al., 2009). For example, activation of the 5‐HT serotonin in the medial frontal cortex has been shown to lead to decreases in the dopamine release in this region. Thus, it is possible that rather than having a direct effect on both of these systems, postweaning social isolation may alter the functioning of one of these systems, which may in turn, lead to disruptions in the functioning of the other system.
Communal rearing as an enriched social environment in rodents.
The standard paradigm used to examine the impact of maternal caregiving on rodent pups’ development is housing the parent and her pups in one room in isolation from other rodents. However, under naturalistic conditions, rodent offspring are more typically reared by multiple female and sometimes male adults. Lactating mothers who rear their offspring in these communal nests were observed to display higher levels of sensitive caregiving such as nursing and licking and grooming behaviors during the postpartum period compared to mothers who reared their offspring alone (see Curley & Champagne, 2016). Compared to offspring reared in standard conditions, offspring reared in communal nests were shown to have more positive outcomes including increased exploratory behaviors, reduced anxiety‐like behaviors, more social behaviors, and increased hippocampal and hypothalamic nerve growth factor (see Curley & Champagne, 2016). The enhanced developmental outcomes of communally reared offspring are likely a function of receiving increased responsive caregiving from mothers and other adults.
The role of temperament in rodent social behaviors and social isolation.
Rodents’ temperament, particularly behavioral inhibition, has been linked with the extent to which they spend their time socially with others and health‐related outcomes. Cavigelli and her colleagues (2009) assessed rats’ behavioral inhibition based on their latency to approach to novelty in both social and nonsocial situations. In social situations, rats were introduced to a novel rat placed in a wired cage; in nonsocial situations, they were introduced to novel objects. They defined behavioral inhibition as longer than median latency to approach to novelty in social and nonsocial situations. Based on this definition, 30% of any tested group showed behavioral inhibition in both situations. Notably, rats’ responses to social situations and nonsocial situations were unrelated: rats could be slow to approach novel social situations but not slow at approaching novel objects. Latency to approach an object in the nonsocial condition was relatively stable across four months, whereas latency to approach an unfamiliar rat in the social condition was not stable over the same time period. Similar to findings in humans, about 17% of rats demonstrated a stable pattern of behavioral inhibition in social situations assessed four months apart, and these inhibited rats continued to show behavioral inhibition at a third time point (for a review see Cavigelli, 2018).
Importantly, behavioral inhibition predicted shortened life span (Cavigelli, 2018). Stable inhibition during social situations, however, was a better predictor of life span than inhibition during nonsocial situations, suggesting that wariness toward unfamiliar peers may be particularly detrimental to health and thus lead to shorter life spans (see Cavigelli, 2018). This may be because social wariness toward unfamiliar peers may increase stress levels, and lead to the “wear and tear” on the body. It is also possible that behaviorally inhibited rats may interact less with other rats and may not effectively use social partners to reduce their stress levels.
There is some evidence suggesting that behavioral inhibition leads to shorter longevity by altering the functioning of the neuroendocrine system. Behaviorally inhibited rats were shown to have 20–30% more basal glucocorticoids than noninhibited rats (Cavigelli et al., 2009), and greater levels of basal glucocorticoids in young adulthood predicted shorter life spans (Cavigelli et al., 2009). Notably, inhibition during social situations was a better predictor of basal glucocorticoid production and glucocorticoid reactivity than inhibition during nonsocial situations, suggesting that wariness in social situations may play an especially important role in altering the basal functioning of the neuroendocrine system. Behavioral inhibition was also associated with poorer cardiovascular system functioning (higher heart rate and blood pressure), which may be another mechanism by which behavioral inhibition may be linked with shorter life span (see Cavigelli, 2018). Finally, behavioral inhibition was associated with poor immune system functioning (an accentuated inflammatory response), which may also explain why this temperament trait