Of the many potential peripheral stress responses, we chose to look specifically at wound healing, as we had previously shown that rats reared in an impoverished environment had substantially worse wound healing and decreased brain activity in a key region of the brain involved in stress response. Furthermore, substantial literature indicates that wound healing is impaired by Crizotinib psychological stress. In humans, female caretakers of Alzheimer patients, women reporting high levels of general life-stress, young adults undergoing an academic exam, couples undergoing marital distress, and patients with pre-existing psychotic illnesses show delayed wound healing. In rodents, restraint stress impairs wound healing and cytokine expression. A few studies have shown that interventions in rodents designed to reduce stress can improve wound healing and abnormal behaviors.. Other studies have shown that physical contact facilitates wound healing. We selected nest building as our EE treatment because isolation reared rats are deprived of normal post-weaning bonding, and a key aspect of bonding for rats involves the nest building by the rat pup’s dam. Specifically, we Vemurafenib examined whether placing Nestlets in cages of isolation reared rats could dampen the negative down stream effects of isolation rearing on wound healing. Nest building with Nestlets is associated with anxiolysis, hippocampal function, reduction of stress hormones, and maternal behavior. To evaluate our hypothesis that the mechanism by which the EE of nest building improves wound healing is central, we gave all isolation reared rats exogenous oxytocin. We then compared the wound healing of animals given Nestlets with those given oxytocin. We reasoned that if the effect of Nestlets on wound healing is centrally mediated through the anxiolytic effects of the Nestlets, then rats treated with oxytocin should have a similar healing response to rats treated with Nestlets. We based this reasoning on the fact that oxytocin, through central mechanisms, enhances social bonding, and through its central effect, has a positive impact on the systemic stress response, and on wound healing. In this study we administered oxytocin intraperitoneally. Because centrally delivered oxytocin receptor antagonists block the effects of peripherally delivered oxytocin, it is likely that peripherally delivered oxytocin acts centrally, even though only a small amount of peripherally administered oxytocin crosses the blood brain barrier.