Reduction in stress-reactivity in rats reared by high-licking dams appears to be mediated by increased glucocorticoid receptor expression in the hippocampus (Liu et al., 1997 and Weaver et al., 2004) which enhances negative feedback on the HPA axis BIBW2992 molecular weight (Sapolsky et al., 1985 and Liu et al., 1997). Recent studies have shown that natural variation in maternal care affects a wide range of outcomes beyond anxiety behavior, including social behaviors. High levels of early maternal grooming are associated with increased play behavior in juvenile male rats (Parent and Meaney, 2008 and Van Hasselt et al., 2012),

increased social interaction in adult offspring of both sexes (Starr-Phillips and Beery, 2014), and altered play dominance rank in adult female rats (Parent et al., 2013). Effects of maternal contact have also been described in other species; for example in prairie voles, maternal care and family structure have been associated with social investigation in adolescence, and changes in parental and mate-directed behaviors in adulthood (Ahern and Young, 2009 and Perkeybile et al., 2013). Early experience of maternal care is sometimes associated with changes in oxytocin and vasopressin system regulation (reviewed in Veenema, 2012), although it is not yet clear whether such changes underlie STI571 the known differences in social behavior. In a synthesis of findings across rodents, primates,

and human studies, Shelly Taylor proposed that in addition to flight-or-flight responses to stress, females show pronounced “tend and befriend” responses to a stressor (Taylor et al., 2000). Taylor related “tending” to parental nurturing behaviors, based on evidence that rat dams lick their pups (tending) following separation, that oxytocin appears to be more

elevated in females following a stressor, and that oxytocin can act both next as an anxiolytic and to promote affiliative behavior. “Befriending” was related to the adaptive value of social support under stressful conditions, and its particular value for females that might be more vulnerable than males. Whether or not shared history of maternal care-giving and defensive social behaviors best explains distinct female responses to stress, the existence of such sex differences in stress/social behavior interactions has been demonstrated repeatedly. We have discussed several examples in this review; first, we described sex differences in the potency of particular stressors, for example crowding is particularly stressful for males, but is either calming to females or does not have major effects on physiological endpoints ( Brown and Grunberg, 1995 and Kotrschal et al., 2007). Even when the same event is stressful to both males and females, the sequelae of stress exposure may differ, for example stress impairs classical conditioning in females, which is the opposite of the effect found in males ( Wood and Shors, 1998).