id="ulink_b95e748d-649f-5a5c-ab0e-f124ef0005f2">Using an adapted version of the human intruder paradigm with three‐ to four‐month‐old rhesus monkeys, Chun and Capitanio (2016) identified behaviorally inhibited monkeys based on three criteria: low emotionality in the first hour following relocation, high vigilance at the end of the 25‐hour separation, and a blunted cortisol response seven hours after relocation/separation. Compared to noninhibited Rhesus, behaviorally inhibited Rhesus were found to spend less time in proximity with their mothers and experience less grooming, even though there were no differences in time of contact with their mothers. Behaviorally inhibited Rhesus infants were also found to spend more time engaging in nonsocial behaviors, such as being alone, as juveniles but not as adults, suggesting that behavioral inhibition in infancy is at least relatively stable from infancy to adolescence. Likewise, duration of nonsocial behaviors was also stable from juvenile years to adulthood (Chun & Capitanio, 2016). These findings suggest that natural variations in behavioral inhibition may contribute to the extent to which Rhesus spend their time nonsocially or perhaps in isolation from other members of their social group.
Kalin and his colleagues conducted a series of studies with Rhesus to examine the neural underpinnings of behavioral inhibition, which they refer to as anxious temperament. They have shown that the central nucleus of the amygdala, anterior hippocampus, and orbitofrontal cortex are key components of a larger complex neural network that underlies anxious temperament (Fox et al., 2008; Fox & Kalin, 2014). For example, Rhesus with higher levels of temperamental anxiety were shown to display more elevated metabolic activity in the central nucleus of the amygdala and anterior hippocampus in stressful and non‐stressful contexts (Fox et al., 2008). Targeted lesions in these brain regions were shown to lead to reductions in temperamental anxiety, suggesting that these brain regions likely play a “causal role” in the expression of anxious temperament (Fox & Kalin, 2014). Given that such targeted lesion studies can only be conducted in animal work, these findings have important implications for our understanding of the causal role of specific brain regions in the expression of socially anxious behaviors.
Based on these findings, a key question is how do these brain regions play a causal role in the expression of anxious temperament? One possibility is that the central nucleus of the amygdala may play a role in the experience of fear and inhibition, whereas the anterior hippocampus and orbitofrontal cortex may regulate the expression of anxiety by providing contextual and regulatory information to the amygdala (Fox & Kalin, 2014). In support of this idea, it was found that the lesions in orbitofrontal cortex led to reduced anxiety (freezing behavior) through an effect on the extended amygdala (Fox et al., 2010). This may be because when orbitofrontal cortex does not send certain contextual messages to the amygdala, the amygdala does not respond to distress to the same extent. These findings suggest that these three brain regions embedded within a larger neural network may influence the expression of anxious temperament not only directly but through their connections with each other. An important implication of these findings for interventions is that treatments that target multiple brain regions associated with anxious temperament might be more effective in treating anxious temperament and preventing social isolation that may occur as a result of socially anxious behavior.
In adult Rhesus, another trait that has been linked with their social experiences is sociability or the tendency to affiliate (Capitanio et al., 2014). In nonhuman primates, high sociability is operationalized by high ratings on warmth and affiliation, and low ratings on solidarity. When studying Rhesus with low sociability, Capitanio and his colleagues (2014) hypothesized that there could be two types of low sociable Rhesus: those that were introverted and those that are lonely. Introverted animals were characterized as those that showed low social attainment and low social initiations, suggesting that they did not attempt to form social connections. On the other hand, lonely animals were those that showed low social attainment but demonstrated high social initiation as the sociable animals. Although the lonely animals showed more social initiations than the introverted animals, they were similar in the extent to which they engaged in complex social behaviors such as “contact” and “initiation of grooming.” In line with the findings with humans (Cacioppo & Hawkley, 2009), the lonely animals were more “sensitive to social threat” such that they showed greater social interest in the “safe” juvenile targets compared to the “risky” targets, whereas the high‐sociable and introverted monkeys did not demonstrate such a preference (see Capitanio, 2017). In another study, it was shown that Rhesus that showed greater perceived social isolation reflected by low sociability and high social threat sensitivity demonstrated a sympathetic nervous system gene expression associated with increased inflammation and reduced antiviral responses (Cole et al., 2015). These findings suggest that lonely Rhesus that frequently initiated interactions but could not succeed in social attainment were more sensitive to social threat and showed poorer health outcomes. In sum, individual differences in Rhesus’ temperamental characteristics such as behavioral inhibition and sociability emerge early in development and are relatively stable across time, and these temperamental characteristics may play a role in the extent to which Rhesus can initiate and engage in successful social interactions and/or spend their time in in isolation from others.
Rodent Models
Why Are Rodent Models Useful?
Although rodents are phylogenetically not as close to humans as primates are, they show many similarities to humans in terms of genetic background, anatomy, physiology, and social life. Given rodents’ shorter life cycle, they allow for examining the effects of early experiences within a couple of weeks, rather than decades. Similar to humans and primates, rodents spend the majority of their postnatal period in close care of their parents (Champagne et al., 2003), which provides opportunities to examine whether and how the absence of these early experiences can lead to disruptions in development. After weaning, most rodents spend a large proportion of their time with peers or other rodents in the community. Thus, their social nature also allows for examining the effects of deprivation of such critical experiences.
Effects of maternal separation and maternal deprivation in rodents.
Early studies of Levine (1960) followed by Meaney’s and his colleagues work (1988) have made a substantial impact to the study of maternal separation and deprivation in rodents. Levine designed one of the first postnatal paradigms used with rodents (i.e., handling) to manipulate the mother–infant relationship. In this paradigm, animals are temporarily removed from their mother and their litter and placed into individual cages for up to 15 minutes until their weaning period (Levine, 1960). Research has linked handling with a range of positive developmental outcomes. It leads to increased intensified maternal care involving licking and grooming behaviors as well as greater infant–mother social interactions, which provide the infant with increased sensory stimulation. This enhanced sensory stimulation, in return, has been shown to lead to increases in the secretion of growth hormones, serotonin and thyroid (Meaney et al., 1988). Compared to non‐handled animals, neonatally handled animals display increased exploration (Weinberg et al., 1978), lower levels of emotional reactivity and fearfulness, lower adrenocortical reactivity in response to novel stimuli, and better spatial learning and memory (Meaney et al., 1988). Likewise, handling has been associated with lower anxiety‐ and depression‐like behaviors in male mice (Liu et al., 1997). Overall, this body of work with rodents suggests that infants’ brief separations from the mother in early development are mostly associated with positive emotional and cognitive outcomes rather than negative outcomes. Brief separations are therefore often considered as “brief immunizations” that allow infants to deal with challenges in a less emotionally reactive and cognitively effective way.
In contrast to the positive effects of handling, longer separations from the mother during infancy have been shown to lead to problematic outcomes. Two main paradigms have been utilized to examine the effects of longer separations from the mother. In maternal separation paradigms, the animals are removed from the litter for about one to eight hours per day (Knop et al., 2017), whereas in social deprivation paradigms, animals are removed for longer durations up to 24 hours per day. Maternal separations for six to eight hours lead to hyper‐responsivity of the neuroendocrine system with