Processing of the oxytocin molecule and its targets. After conversion from the prohormone form, oxytocin exists in an extended form with three extra amino acids. The conversion from extended OXT to oxytocin consisting of nine amino acids occurs with maturation of the hypothalamus in neurotypical individuals. It is not known how this extended form interacts with receptors. In their canonical nine–amino acid forms, both oxytocin and vasopressin bind and act as agonists to both OXTR and AVPR1A, although oxytocin has a higher affinity for OXTR than the AVPR1A, as denoted by the thicker arrow. Oxytocin also acts as an agonist to the pain-sensing transient receptor potential vanilloid-1 (TRPV1) receptor and as a positive allosteric modulator at the MOR. After degradation by IRAP, the C-terminal tail is cleaved from oxytocin to form MIF-1, which can both inhibit MOR and act as an allosteric modulator on the D2 subtype of dopamine receptors (D₂R). Oxytocin can also be degraded by other as of yet unspecified peptidase activity into a linear form that stimulates activity of the α-2 type adrenoreceptors (α2ARs). Conventional arrow = agonist; circle-tipped arrow = positive allosteric modulator; block-tipped arrow = antagonist.

The effects of oxytocin and vasopressin can be context-dependent. Sensitivity of the AVPR1A or OXTR to either oxytocin or vasopressin may be altered by a history of adversity or by positive experiences, especially during early life. For example, as illustrated here, arousal or stress may increase the release of oxytocin and/or increase sensitivity of AVPR1A to oxytocin [reviewed Carter (2017)].

Oxytocin acts as an anti-inflammatory molecule for the nervous system in the presence of stressors. For the developing brain, oxytocin confers neuroprotection in the presence of a stressor by inhibiting the release of proinflammatory cytokines by microglia by decreasing oxidative stress exposure and by protecting mitochondrial function. For the adult brain, oxytocin confers similar neuroprotection in the presence of a stressor by inhibiting the release of proinflammatory cytokines by microglia, by decreasing oxidative stress exposure, by protecting mitochondrial function, and by increasing antioxidant capacity. Moreover, similar to its inhibition of microglia-mediated inflammatory cascades, oxytocin inhibits macrophage-mediated proinflammatory cascades outside of the central nervous system during an immune challenge with LPS. Although oxytocin mediates many aspects of social behavior and cognition, the known social and cognitive functions that oxytocin protects in the presence of inflammation are shown here for the developing and adult brain. Inflammatory cascades are shown in purple and oxytocin signaling is shown in red. All of oxytocin’s protective effects shown here are believed to be mediated by oxytocin binding to the OXTR. COX-2, cyclooxygenase-2; GPx, glutathione peroxidase; GSH, reduced glutathione; GSSG, oxidized glutathione; HMGB1, high-mobility group box 1.